Methods of preparing sulfinamides and sulfoxides

ABSTRACT

This invention encompasses novel methods of preparing sulfinamides and sulfoxides, particularly stereomerically pure sulfinamides and sulfoxides. The invention further encompasses novel compounds from which sulfinamides and sulfoxides can be prepared.

[0001] This application claims priority to U.S. Provisional ApplicationNo. 60/283,337, filed Apr. 13, 2001, the entirety of which isincorporated herein by reference.

1. FIELD OF THE INVENTION

[0002] This invention relates to sulfinamides and sulfoxides, methods oftheir preparation, and compounds that can be used to prepare them.

2. BACKGROUND OF THE INVENTION 2.1. The Asymmetric Synthesis of Amines

[0003] At least 75% of drugs and drug candidates reportedly incorporateamine functionality. Tang, T. P. and Ellman, J. A., J. Org. Chem.64:12-13 (1999). The asymmetric synthesis of amines is consequently ofparticular importance to the pharmaceutical industry.

[0004] One method that reportedly can be used to prepare opticallyactive α-amino acids is disclosed in International Application WO2000/041997. According to this method, a compound of the formulaRaC*H(OH)—C*H(Rb)Rc, wherein Rc can be R₁SO₂(R₂)N— and the asterisksignifies a chiral center, is reportedly prepared by reacting anα-aminocarbonyl compound of the formula Ra—CO—CH(Rb)—Rc with hydrogen ora hydrogen donor in the presence of an optically active transition metalcompound and a base.

[0005] Another recently reported method of preparing chiral amino acidsutilizes sulfinamides. See, e.g., Tang, T. P. and Ellman, J. A., J. Org.Chem. 64:12-13 (1999); Cogen, D. A., et al., Tetrahedron 55:8883-8904(1999); Liu, G., et al., J. Am. Chem. Soc. 119:9913-9914 (1997); Davis,F. A. and McCoull, W., J. Org. Chem. 64:3396-3397 (1999). In an exampleof this method, tert-butanesulfinamide condenses with aldehydes andketones to give tert-butanesulfinyl imines in high yields. Tang, T. P.and Ellman, J. A., J. Org. Chem. 64:12-13 (1999). These imines can thenbe contacted with Grignard reagents or organolithiums to provide theintermediate shown below in Scheme I, which can then be subjected toacidic methanolysis to provide an a-branched amine-hydrochlorideproduct. Id.

[0006] Few methods of preparing enantiomerically pure sulfinamides havebeen reported. See, e.g., Cogan, D. A., et al., J. Am. Chem. Soc.120:8011-8019 (1998); Liu, G., et al., J. Am. Chem. Soc. 119:9913-9914(1997). In one method, tert-butanesulfinamide is prepared byasymmetrically oxidizing tert-butyl disulfide to provide anintermediate, which is then cleaved by reaction with LiNH₂. Liu, G., etal., J. Am. Chem. Soc. 119:9913-9914 (1997). Unfortunately, theenantiomeric purity of the resulting sulfinamide reportedly does notexceed 91%. Id. The method is further limited in that it can be used forthe synthesis of only a few different kinds of sulfinamides, of whichtert-butanesulfinamide is an example. In addition, this method is notamenable to large-scale, or industrial, production of sulfinamides. Aneed therefore exits for more efficient and effective methods ofpreparing a wide variety of sulfinamides, particularly enantiomericallypure sulfinamides. A need further exists for a method of preparingsulfinamides that can be adapted to an industrial scale.

2.2. The Asymmetric Synthesis of Sulfoxides

[0007] The synthesis of chiral sulfoxides is also important to thepharmaceutical industry. For example, a variety of pharmacologicallyactive benzimidazoles and structurally related sulfoxide compoundscontain a stereogenic sulfur atom. Examples of such compounds are shownbelow in racemic form:

[0008] Pantoprazole sodium is sold under the tradename Protonix® for theshort term treatment of erosive esophagitis associated withgastroesophageal reflux disease (GERD). Physicians' DeskReference,3439-3442 (55^(th) ed., 2001). Lansoprazole is sold under the tradenamePrevacide for the short term treatment of active duodenal ulcer. Id. at3189-3194. Omeprazole, which is also indicated for the short termtreatment of active duodenal ulcer, is sold under the tradenamePrilosec®. Id. at 587-591. Finally, rabeprazole is sold under thetradename Aciphex® for the short term treatment of erosive or ulcerativeGERD, for maintaining healing and reduction in relapse rates ofheartburn symptoms in patients with erosive or ulcerative GERD, for theshort-term healing of active duodenal ulcer, and for the long-termtreatment of pathological hypersecretroy conditions. Id. at 1178-1181.

[0009] Various attempts have been made to obtain enantiomerically pureforms of sulfoxide compounds such as these. Initial attempts relied onchromatography and the formation of chiral salts. See, e.g., U.S. Pat.Nos. 5,693,818 and 5,714,504. Methods for the asymmetric syntheses ofsulfoxides have also been alleged. For example, U.S. Pat. No. 5,776,765discloses a process that can allegedly be used for the enantiomericsynthesis of omeprazole, which comprises the use of a microbial enzymesystem to enantioselectively reduce a racemic sulfoxide compound. See,e.g., col. 12, line 57- col. 13, line 67. A method disclosed by U.S.Pat. No. 5,948,789 comprises the oxidation of a pro-chiral sulphideusing a chiral titanium complex and a base. See, e.g., col. 25, line64-col. 27, line 8.

[0010] A need exists for new methods of preparing stereomerically pure(e.g., enantiomerically pure) sulfoxides. A particular need exists forefficient and effective methods of preparing enantiomerically puresulfoxides that can be adapted to an industrial scale.

3. SUMMARY OF THE INVENTION

[0011] This invention is directed, in part, to novel methods ofpreparing sulfinamides and sulfoxides, particularly stereomerically puresulfinamides and sulfoxides. The invention further encompasses novelcompounds from which sulfinamides and sulfoxides can be prepared.Compounds of this invention can be used in the preparation ofbiologically active (e.g., pharmacologically active) compounds, or arethemselves biologically active and useful in the treatment or preventionof diseases or conditions in animals (e.g., humans).

3.1. Definitions

[0012] As used herein, the term “prodrug” means a derivative of acompound that can hydrolyze, oxidize, or otherwise react underbiological conditions (in vitro or in vivo) to provide the compound.Examples of prodrugs include, but are not limited to, derivatives of2-(2-pyridylmethyl)sulfinyl)benzimidazoles that comprise biohydrolyzablemoieties such as biohydrolyzable amides, biohydrolyzable esters,biohydrolyzable carbamates, biohydrolyzable carbonates, biohydrolyzableureides, and biohydrolyzable phosphate analogues. Other examples ofprodrugs include derivatives of2-(2-pyridyhnethyl)sulfinyl)benzimidazoles that comprise —NO, —NO₂,—ONO, and —ONO₂ moieties.

[0013] As used herein, the terms “biohydrolyzable carbamate,”“biohydrolyzable carbonate,” “biohydrolyzable ureide,” “biohydrolyzablephosphate” mean a carbamate, carbonate, ureide, or phosphate,respectively, of a compound that either: 1) does not interfere with thebiological activity of the compound but can confer upon that compoundadvantageous properties in vivo, such as uptake, duration of action, oronset of action; or 2) is biologically less active or inactive but isconverted in vivo to the biologically active compound. Examples ofbiohydrolyzable carbamates include, but are not limited to, loweralkylamines, substituted ethylenediamines, aminoacids,hydroxyalkylamines, heterocyclic and heteroaromatic amines, andpolyether amines.

[0014] As used herein, the term “biohydrolyzable ester” means an esterof a compound that either: 1) does not interfere with the biologicalactivity of the compound but can confer upon that compound advantageousproperties in vivo, such as uptake, duration of action, or onset ofaction; or 2) is biologically less active or inactive but is convertedin vivo to the biologically active compound. Examples of biohydrolyzableesters include, but are not limited to, lower alkyl esters, acyl esters(e.g., —C(O)Z, wherein Z is F, C, Br, I), alkoxyacyloxy esters, alkylacylamino alkyl esters, and choline esters.

[0015] As used herein, the term “biohydrolyzable amide” means an amideof a compound that either: 1) does not interfere with the biologicalactivity of the compound but can confer upon that compound advantageousproperties in vivo, such as uptake, duration of action, or onset ofaction; or 2) is biologically less active or inactive but is convertedin vivo to the biologically active compound. Examples of biohydrolyzableamides include, but are not limited to, lower alkyl amides, a-amino acidamides, alkoxyacyl amides, substituted and unsubstituted ureas, andalkylaminoalkylcarbonyl amides.

[0016] As used herein, the term “pharmaceutically acceptable salt”refers to a salt prepared from a pharmaceutically acceptable non-toxicinorganic or organic acid. Suitable non-toxic acids include, but are notlimited to, acetic, benzenesulfonic, benzoic, camphorsulfonic, citric,ethenesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric,isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic,nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric,and p-toluenesulfonic acids. For example, specific pharmaceuticallyacceptable salts are hydrochloride, maleic acid, and tartaric acidsalts.

[0017] As used herein and unless otherwise indicated, the term “alkyl”includes saturated linear, branched, and cyclic hydrocarbon radicalshaving 1 to 20 carbon atoms, 1 to 12, 1 to 8, or 1 to 4 carbon atoms. Analkyl group can include one or more double or triple bonds or can besubstituted with one or more heteroatoms or halogens (e.g., F, Cl, Br,I). It is understood that cyclic alkyl groups comprise at least threecarbon atoms. Specific examples of branched alkyl have one or twobranches. Unsaturated alkyl have one or more double bonds and/or one ormore triple bonds. Specific examples of unsaturated alkyl have one ortwo double bonds or one triple bond. Alkyl chains may be unsubstitutedor substituted with from 1 to 4 substituents. Specific examples ofsubstituted alkyl are mono-, di-, or trisubstituted alkyl. Specificexamples of alkyl substituents include halo, haloalkyl, hydroxy, aryl(e.g., phenyl, tolyl, alkyloxphenyl, alkyloxycarbonylphenyl,halophenyl), beterocyclyl, and heteroaryl.

[0018] As used herein and unless otherwise indicated, the term “loweralkyl” means branched or linear alkyl having from 1 to 8 or from 1 to 4carbon atoms. Examples include, but are not limited to, methyl, ethyl,propyl, isopropyl, isobutyl, and tertiary butyl.

[0019] As used herein and unless otherwise indicated, the term“heteroalkyl” means a saturated or unsaturated chain containing carbonand at least one heteroatom, wherein no two heteroatoms are adjacent.Heteroalkyl chains contain from 1 to 18, 1 to 12, 1 to 6, or 1 to 4member atoms (carbon and heteroatoms) in the chain. Heteroalkyl chainsmay be straight or branched. Specific examples of branched heteroalkylhave one or two branches. Unsaturated heteroalkyl have one or moredouble bonds and/or one or more triple bonds. Specific examples ofunsaturated heteroalkyl have one or two double bonds or one triple bond.Heteroalkyl chains may be unsubstituted or substituted with from 1 toabout 4 substituents. Specific examples of heteroalkyl are substitutedor unsubstituted. Specific examples of heteroalkyl substituents includehalo, hydroxy, aryl (e.g., phenyl, tolyl, alkyloxphenyl,alkyloxycarbonylphenyl, halophenyl), heterocyclyl, and heteroaryl. Forexample, alkyl substituted with the following substituents areheteroalkyl: alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, pentoxy),aryloxy (e.g., phenoxy, chlorophenoxy, tolyloxy, methoxyphenoxy,benzyloxy, alkyloxycarbonylphenoxy, acyloxyphenoxy), acyloxy (e.g.,propionyloxy, benzoyloxy, acetoxy), carbamoyloxy, carboxy, mercapto,alkylthio, acylthio, arylthio (e.g., phenylthio, chlorophenylthio,alkylphenylthio, alkoxyphenylthio, benzylthio,alkyloxycarbonylphenylthio), amino (e.g., amino, mono- and di- C₁-C₃alkanylamino, methylphenylamino, methylbenzylamino, C₁-C₃ alkanylamido,carbamamido, ureido, guanidino).

[0020] As used herein and unless otherwise indicated, the term“heteroatom” includes a nitrogen, sulfur, oxygen, or phosphorus atom.Groups containing more than one heteroatom may contain differentheteroatoms.

[0021] As used herein and unless otherwise indicated, the term “aryl”includes an organic radical derived from an aromatic hydrocarbon byremoval of one hydrogen, such as phenyl or naphthyl. Aryl rings aremonocyclic or fused bicyclic ring systems. Monocyclic aromatic ringscontain from about 5 to about 10 carbon atoms, from 5 to 7 carbon atoms,or from 5 to 6 carbon atoms in the ring. Bicyclic aromatic rings containfrom 8 to 12 carbon atoms, or 9 or 10 carbon atoms in the ring. Aromaticrings may be unsubstituted or substituted with from 1 to about 4substituents on the ring. Specific examples of aromatic ringsubstituents include: halo, cyano, alkyl, heteroalkyl, haloalkyl,phenyl, phenoxy or any combination thereof. More Specific examples ofsubstituents include halo and haloalkyl. Specific examples of aromaticrings include naphthyl and phenyl.

[0022] As used herein and unless otherwise indicated, the term “aralkyl”means an aryl substituted with one or more linear, branched, or cyclicalkyl groups. Aralkyl moieties can be attached to other moieties throughtheir aryl or alkyl components.

[0023] As used herein and unless otherwise indicated, the term “ether”includes alkyl groups wherein at least one carbon atom has been replacedwith an oxygen atom, and aralkyl groups wherein at least onenon-aromatic carbon atom has been replaced with an oxygen atom.

[0024] As used herein and unless otherwise indicated, the terms“heterocyclic group” and “heterocycle” include aromatic and non-aromaticheterocyclic groups containing one or more heteroatoms each selectedfrom O, S, N, or P. Non-aromatic heterocyclic groups include groupshaving only 3 atoms in their ring system, but aromatic heterocyclicgroups (i.e., heteroaryl groups) must have at least 5 atoms in theirring system. Heterocyclic groups include benzo-fused ring systems andring systems substituted with one or more oxo moieties. An example of a4 membered heterocyclic group is azetidinyl (derived from azetidine). Anexample of a 5 membered heterocyclic group is thiazolyl, and an exampleof a 10 membered heterocyclic group is quinolinyl. Examples ofnon-aromatic heterocyclic groups include, but are not limited to,pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl,tetrahydrothiopyranyl, piperidino, morpholino, thiomorpholino,thioxanyl, piperazinyl, azetidinyl, oxetanyl, thietanyl,homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl,thiazepinyl, 1,2,3,6-tetrahydropyridinyl, 2-pyrrolinyl, 3-pyrrolinyl,indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl,pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl,dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl,3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, 3H-indolyl,quinolizinyl, and substituted derivative thereof. Examples of aromaticheterocyclic groups include, but are not limited to, pyridinyl,methylpyridine analgoues, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl,pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl,isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl,benzimidazolyl, benzoimidazoles, benzofuranyl, cinnolinyl, indazolyl,indolinyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl,isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl,benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl,quinazolinyl, quinoxalinyl, naphthyridinyl, furopyridinyl, andsubstituted derivatives thereof. The foregoing groups, as derived fromthe compounds listed above, may be C-attached or N-attached where such-attachment is possible. For instance, a group derived from benzimidazolcan be -benzimidazol-1-yl (N-attached) or benzimidazol-2-yl(C-attached).

[0025] As used herein and unless otherwise indicated, the term“heteroaryl” means an aromatic heterocycle. A heteroaryl is an aromaticring system containing carbon and from 1 to about 4 heteroatoms in thering. Heteroaromatic rings are monocyclic or fused bicyclic ringsystems. Monocyclic heteroaromatic rings contain from about 5 to about10, from 5 to 7, or from 5 to 6 member atoms (carbon and heteroatoms).Bicyclic heteroaromatic rings contain from 8 to 12 9 or 10 member atoms.Heteroaromatic rings may be unsubstituted or substituted with from 1 toabout 4 substituents on the ring. Specific examples of heteroaromaticring substituents include: halo, cyano, alkyl, heteroalkyl, haloalkyl,phenyl, phenoxy or any combination thereof. More Specific examples ofsubstituents include halo, haloalkyl, and phenyl. Specific examples ofheteroaromatic rings include thienyl, thiazolo, purinyl, pyrimidyl,pyridyl, and furanyl.

[0026] As used herein and unless otherwise indicated, the term “sulfide”includes alkyl groups wherein at least one carbon atom has been replacedwith a sulfur atom, and aralkyl groups wherein at least one non-aromaticcarbon atom has been replaced with a sulfur atom.

[0027] As used herein and unless otherwise indicated, the term“substituted” as used to describe a compound or chemical moiety meansthat at least one hydrogen atom of that compound or chemical moiety isreplaced with a second chemical moiety. Examples of second chemicalmoieties include, but are not limited to: halogen atoms (e.g., chlorine,bromine, and iodine); C₁-C₆ linear, branched, or cyclic alkyl (e.g.,methyl, ethyl, butyl, tert-butyl, and cyclobutyl); hydroxyl; thiols;carboxylic acids; esters, amides, silanes, nitriles, thioethers,stannanes, and primary, secondary, and tertiary amines (e.g., —NH₂,—NH(CH₃), —N(CH₃)₂, and cyclic amines). Specific examples of secondchemical moieties are chlorine, hydroxyl, methoxy, amine, thiol, andcarboxylic acid.

[0028] As used herein and unless otherwise indicated, a composition thatis “substantially free” of a compound means that the compositioncontains less than about 20% by weight, more preferably less than about10% by weight, even more preferably less than about 5% by weight, andmost preferably less than about 3% by weight of the compound.

[0029] As used herein and unless otherwise indicated, the term“stereomerically pure” means a composition that comprises onestereoisomer of a compound and is substantially free of otherstereoisomers of that compound. For example, a stereomerically purecomposition of a compound having one chiral center will be substantiallyfree of the opposite enantiomer of the compound. A stereomerically purecomposition of a compound having two chiral centers will besubstantially free of other diasteroemers of the compound. A typicalstereomerically pure compound comprises greater than about 80% by weightof stereoisomer of the compound and less than about 20% by weight ofother stereoisomers the compound, more preferably greater than about 90%by weight of one stereoisomer of the compound and less than about 10% byweight of the other stereoisomers of the compound, even more preferablygreater than about 95% by weight of one stereoisomer of the compound andless than about 5% by weight of the other stereoisomers of the compound,and most preferably greater than about 97% by weight of one stereoisomerof the compound and less than about 3% by weight of the otherstereoisomers of the compound.

[0030] As used herein and unless otherwise indicated, the term“enantiomerically pure” means a stereomerically pure composition of acompound having one chiral center.

[0031] As used herein and unless otherwise indicated, the term “polymerbound” and “polymer bound alkyl or aryl” mean that the compound of theinvention is covalently bound to a polymer support, such as, but notlimited to, Merrifield Resin, See Wang et al., J. Org. Chem, 1977, 42,1286-1290; Wang Resin, See Fancelli et al., Tetrahedron Lett., 1997, 38,2311-2314; Aminomethyl Resin; MBHA Resin; Amino Acid-2-ChlorotritylResin; Carboxypolystyrene; 4-Nitrophenyl Carbonate Resin; Oxime Resin;Safety-Catch Resin; Alkenyl based resins; Br, Cl functionalized resins;Carbonate resins; CHO functionalized resins; CO₂H functionalized resins;Diazonium-based resins; Enol functionalized resins; NH₂, NH₂NHfunctionalized resins; OH functionalized resins; Orthogonalphotocleavable resins; SH functionalized resins; Silylalkyl resins;Silyloxy resins; Triazene-based resins; Polymer-bound bases (e.g.,(Polystyrylmethyl)trimethylammonium bicarbonate, Morpholinomethylpolystyrene HL, Piperazinomethyl polystyrene, Piperidine-4-carboxylicacid polyamine resin, Piperidinomethyl polystyrene, TBD-methylpolystyrene, Tris-(isonipecotylaminoethyl)-amine polystyrene);Polymer-bound coupling reagents (e.g., Ethoxycarbonylazocarboxymethylpolystyrene, HOBt-6-carboxamidomethyl polystyrene,N-Cyclohexylcarbodiimide, N′-methyl polystyrene); Polymer-boundoxidizing reagents (e.g., Polystyrylmethyl)trimethylammoniummetaperiodate, (Polystyrylmethyl)trimethyl-ammonium perruthenate,4-(Polystyrylmethyloxy)-2,2,6,6-tetramethyl-piperidin-1-yloxy freeradical, 6-(Methylsulfinyl)hexanoylmethyl polystyrene, TEMPOpolystyrene); Polymer-bound phosphines (e.g., Di(n-butyl)phenylphosphinepolystyrene, Di-o-tolylphenylphosphine polystyrene,Dicyclohexylphenylphosphine polystyrene, DiphenylphosphinobenzoylNovaGel™ AM resin, Diphenylphosphinomethyl polystyrene,Diphenylphosphinopolystyrene, Triphenylphosphine NovaGel™,Triphenylphosphine polystyrene); or Polymer-bound reducing agents (e.g.,(Polystyrylmethyl)trimethylammonium borohydride,(Polystyrylmethyl)trimethylammonium cyanoborohydride, Dimethylsilylpolystyrene).

[0032] It should be noted that if there is a discrepancy between adepicted structure and a name given that structure, the depictedstructure is to be accorded more weight. In addition, if thestereochemistry of a structure or a portion of a structure is notindicated with, for example, bold or dashed lines, the structure orportion of the structure is to be interpreted as encompassing allstereoisomers of it.

4. DETAILED DESCRIPTION OF THE INVENTION

[0033] This invention is directed, in part, to novel methods ofpreparing sulfinamides and sulfoxides. These methods can be used, forexample, to provide sulfinamides such as, but riot limited to,stereomerically pure forms of tert-butanesulfinamide, and sulfoxidessuch as, but not limited to, stereomerically pure forms of compoundsdisclosed by U.S. Pat. Nos. 5,776,765 (e.g.,2-(2-pyridylmethyl)sulfinyl)benzimidazoles) and 5,945,425 (e.g.,(H⁺/K⁺)ATPase inhibitors), both of which are incorporated herein byreference.

[0034] A first embodiment of the invention encompasses a method ofpreparing a sulfinamide or sulfoxide, which comprises contacting acompound of Formula 1:

[0035] wherein n is 0 to 3; L is CO_(m)R₃ or SO_(m)R₃, wherein m is 0 to3; R₁ and R₂ together form a cyclic structure (e.g., substituted orunsubstituted heterocycle or aryl) or each of R₁ and R₂ is independentlysubstituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted aryl, substituted or unsubstituted heterocycle; R_(1′) andR_(2′) together form a cyclic structure or each of R_(1′) and R_(2′) isindependently hydrogen, substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aryl, or substituted or unsubstitutedheterocycle; R_(a) and R_(b) together form a cyclic structure or each ofR_(a) and R_(b) is independently hydrogen, substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted heteroalkyl, substituted or unsubstituted aryl, orsubstituted or unsubstituted heterocycle; and each of R₃ and X isindependently a polymer bound alkyl, aryl or heteroalkyl, substituted orunsubstituted alkyl, substituted or unsubstituted aralkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstituted ester,substituted or unsubstituted ketone, substituted or unsubstitutedphosphonate, substituted or unsubstituted phosphonic acid ester,substituted or unsubstituted phosphinoyl (e.g., —P(═O)(R₁)₃; wherein R₁is defined above), substituted or unsubstituted sulfide, substituted orunsubstituted sulfone, substituted or unsubstituted sulfinyl imine(e.g., —S(═O)(═NR₁)—R₂ wherein R₁ and R₂ are defined above), substitutedor unsubstituted heterocycle, or —NR₄R₅, wherein R₄ and R₅ together withthe nitrogen atom to which they are attached form a heterocycle or eachof R₄ and R₅ is independently hydrogen, substituted or unsubstitutedalkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle;

[0036] with a compound of the formula MY, wherein M is a metal or metalcomplex capable of transferring Y to the positively charged sulfur atomof the compound of Formula 1 and Y is independently substituted orunsubstituted alkyl, substituted or unsubstituted aralkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstituted ester,substituted or unsubstituted ketone, substituted or unsubstitutedphosphonate, substituted or unsubstituted phosphonic acid ester,substituted or unsubstituted phosphinoyl, substituted or unsubstitutedsulfide, substituted or unsubstituted sulfone, substituted orunsubstituted sulfinyl imine, substituted or unsubstituted heterocycle,or is of the formula —NR₆R₇, wherein R₆ and R₇ together with thenitrogen atom to which they are attached form a heterocycle or each ofR₆ and R₇ is independently a polymer bound alkyl, aryl or heteroalkyl;hydrogen; substituted or unsubstituted alkyl; substituted orunsubstituted aralkyl; substituted or unsubstituted heteroalkyl;substituted or unsubstituted aryl; substituted or unsubstituted ether;substituted or unsubstituted ester; substituted or unsubstituted ketone;substituted or unsubstituted phosphonate; substituted or unsubstitutedphosphonic acid ester; substituted or unsubstituted phosphinoyl;substituted or unsubstituted sulfide; substituted or unsubstitutedsulfone; substituted or unsubstituted sulfinyl imine; substituted orunsubstituted heterocycle; under conditions suitable for the formationof a compound of Formula 2:

[0037] wherein X and Y are defined above.

[0038] In a preferred method of this embodiment, the compound(s) ofFormula 1 and/or Formula 2 is/are stereomerically pure.

[0039] In another preferred embodiment, the compounds of Formula 1 havethe following structures:

[0040] In another method of this embodiment, M of the formula MY is Al,Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, or Cu; in another method, M is of theformula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ, or CuZ, wherein Z is Cl, Br,I, aryl, aralkyl, or heterocycle.

[0041] In another method, the compound of Formula 1 is prepared bycontacting a compound of Formula 3:

[0042] wherein n is 0 to 3; L is CO_(m)R₃ or SO_(m)R₃, wherein m is 0 to3; and R₁, R₂, R_(1′), R_(2′), and R₃ are defined above;

[0043] with a compound of the formula M′X, wherein M′ is a metal ormetal complex capable of transferring X to the positively charged sulfuratom of the compound of Formula 3 and X is defined above.

[0044] In a preferred embodiment, the compounds of Formula 3 have thefollowing structures:

[0045] In a preferred method of this embodiment, M′ of the formula M′Xis Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, or Cu; in another method, M′is of the formula CdZ′, BaZ′, MgZ′, ZnlZ′, AlZ′₂, MnZ′, InZ′, or CuZ′,wherein Z′ is Cl, Br, I, aryl, aralkyl, or heterocycle or a combinationwith a Lewis acid, such as, but not limited to, Ti(OPr)₄ or Ti(OR₁)₃Cl,where R₁ is defined above.

[0046] In another preferred method of this embodiment, X is tert-butyl,trialkylmethyl, triheteroalkylmethyl, triarylmethyl,triheteroaryhnethyl, triheterocyclemethyl, aryl, heterocyclic,heteroaryl, alkyltrialkyl, alkylheteroalkylmethyl, diarylalkylmethyl,adamantyl, dialkyladamantyl, trialkylaryl, triethylmethyl,dimethylethyl, trimethylphenyl, trialkylphenyl, triisopropylphenyl,polymer bound alkyl or aryl or is of Formula 4: or is of Formula 4:

[0047] or a salt thereof, wherein each R₈ is independently substitutedor unsubstituted alkyl, substituted or unsubstituted aralkyl,substituted or unsubstituted heteroalkyl, substituted or unsubstitutedaryl, substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, a primary, secondary,or tertiary amine, or a halogen atom; and p is an integer of 0 to 4; oris of Formula 5:

[0048] wherein each R₉ is independently substituted or unsubstitutedalkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, substitutedor unsubstituted heterocycle, a primary, secondary, or tertiary amine,or a halogen atom; and q is an integer of 0 to 4. Preferably, q is 2 or3.

[0049] If X is of Formula 4, p is preferably 0 or 1. If p is 1, R₈ ispreferably —OCH₃ or —OCHF₂. If X is of Formula 5 and q is 2, each R₉ ispreferably —CH₃, —OCH₃, —OCH₂CF₃, or —OC₅H₁₁; if q is 3, R₉ ispreferably —CH₃ or —OCH₃.

[0050] In another preferred method of this embodiment, Y is —NR₆R₇ or isof Formula 4 or Formula 5. If Y is of Formula 4, p is preferably 0 or 1.If p is 1, R₈ is preferably —OCH₃ or —OCHF₂. If Y is of Formula 5 and qis 2, each R₉ is preferably —CH₃, —OCH₃, —OCH₂CF₃, or —OC₅H₁₁; if q is3, R₉ is preferably —CH₃ or —OCH₃.

[0051] In another preferred method of this embodiment, R₁ is aryl oraklyl. In a more preferred method, R₁ is methyl.

[0052] In another preferred method of this embodiment, R₂ is aryl oralkyl. In a more preferred method, R₂ is phenyl.

[0053] In another preferred method of this embodiment, R₃ is asubstituted or unsubstituted heteroalkyl, substituted or unsubstitutedlower alkyl (e.g., halogenated phenyl, 3-methylphenyl, 4-methylphenyl,1,3,5-trimethylphenyl, (tert-butyl)phenyl, 2-mesityl, tolyl, or1,3,5-triisopropylphenyl), or aryl (e.g., phenyl and biphenyl). In amore preferred method, R₃ is 2-mesityl, tolyl, tri-isopropyl, or apolymer bound aryl or alkyl.

[0054] In a preferred method of this embodiment, the compound of Formula1 is stereomerically pure and has one of the followingstereochemistries:

[0055] In another preferred method of this embodiment, the compound ofFormula 1 has one of the following structures:

[0056] wherein X and R₃ are each defined above and each R₁₀ isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, a primary,secondary, or tertiary amine, a heterocycle, or a halogen atom; n is aninteger of 1 to 4; and m is an integer of 0 to 4. In a preferred method,n is 1 and m is 0, 1, or 2, and wherein R₃ is tert-butyl,trialkylmethyl, triheteroalkylmethyl, triarylmethyl,triheteroarylmethyl, triheterocyclemethyl, aryl, heterocyclic,heteroaryl, alkyltrialkyl, alkylheteroalkylmethyl, diarylalkylmethyl,adamantyl, dialkyladamantyl, trialkylaryl, triethylmethyl,dimethylethyl, trimethylphenyl, trialkylphenyl, triisopropylphenyl,polymer bound alkyl or aryl or is of Formula 4:

[0057] or a salt thereof, wherein each R₈ is independently substitutedor unsubstituted alkyl, substituted or unsubstituted aralkyl,substituted or unsubstituted aryl, substituted or unsubstituted ether,substituted or unsubstituted sulfide, substituted or unsubstitutedheterocycle, a primary, secondary, or tertiary amine, or a halogen atom;and p is an integer of 0 to 4; or is of Formula 5:

[0058] wherein each R₉ is independently substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, substituted or unsubstituted heterocycle, aprimary, secondary, or tertiary amine, or a halogen atom; and q is aninteger of 0 to 4. In a preferred method, the compound of Formula 6 or 7is stereomerically pure.

[0059] In a preferred method of this embodiment, the compound of Formula2 is of Formula 8, stereoisomers of which are shown below:

[0060] In a particularly preferred method of this embodiment, X isphenyl, 4-methylphenyl, tert-butyl, adamantyl, trimethylphenyl, pyridyl,or trialkylmethyl, triisopropylphenyl, trialkyl phenyl, tetraacylphenyl,or pentaalkylphenyl, triheteroalkylmethyl, triarylmethyl,triheteroarylmethyl, triheterocyclemethyl, aryl, heterocyclic,heteroaryl, alkyltrialkyl, alkylheteroalkylmethyl, diarylalkylmethyl,dialkyladamantyl, trialkylaryl, triethylmethyl, dimethylethyl,trialkylphenyl, triisopropylphenyl, polymer bound alkyl or aryl or is ofFormula 4:

[0061] or a salt thereof, wherein each R₈ is independently substitutedor unsubstituted alkyl, substituted or unsubstituted aralkyl,substituted or unsubstituted aryl, substituted or unsubstituted ether,substituted or unsubstituted sulfide, substituted or unsubstitutedheterocycle, a primary, secondary, or tertiary amine, or a halogen atom;and p is an integer of 0 to 4; or is of Formula 5:

[0062] wherein each R₉ is independently substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, substituted or unsubstituted heterocycle, aprimary, secondary, or tertiary amine, or a halogen atom; and q is aninteger of 0 to 4. In another preferred method, at least one of R₆ andR₇ is hydrogen. In yet another preferred method, R₆ and R₇ are bothhydrogen.

[0063] In another preferred method of this embodiment, the compound ofFormula 3 has one of the following stereochemistries:

[0064] In a particularly preferred method of this embodiment, thecompound of Formula 3 has one of the following structures:

[0065] wherein R₃, R₁₀, m, and n are defined herein.

[0066] With regard to compound 10, when n is 1, the stereochemistry ofthe compound is preferably cis, two isomers of which are shown below:

[0067] A specific method of this embodiment is a method of preparingpantoprazole, or a derivative, prodrug, salt, solvate, clathrate, orstereomerically pure form thereof, which comprises contacting a compoundof Formula 11:

[0068] wherein R₁, R₂, R_(1′), and R_(2′) are defined herein, and Protis a protecting group (e.g., an aminal or sulfanamide), with a compoundof Formula 12:

[0069] wherein M is defined herein, under conditions suitable for theformation of a compound of Formula 13:

[0070] and optionally contacting the compound of Formula 13 with areagent capable of replacing Prot with a hydrogen atom or a cation(e.g., Na⁺ or K⁺). Suitable reagents include, but are not limited toNaOH, KOH, or a mild acid followed by NaH or KH.

[0071] In a preferred method, the compound of Formula 11 is prepared bycontacting a compound of Formula 3 with a compound of Formula 14:

[0072] wherein M′ is defined herein, under conditions sufficient for theformation of the compound of Formula 11.

[0073] In another preferred method, the compounds of formulas 11 and 13are enantiomerically pure.

[0074] Another specific method of this embodiment is a method ofpreparing lansoprazole, or a derivative, prodrug, salt, solvate,clathrate, or stereomerically pure form thereof, which comprisescontacting a compound of Formula 15:

[0075] wherein R₁, R₂, R_(1′), R_(2′), and Prot are defined herein, witha compound of Formula 16:

[0076] wherein M is defined herein, under conditions suitable for theformation of a compound of Formula 17:

[0077] and optionally contacting the compound of Formula 17 with areagent capable of replacing Prot with a hydrogen atom or a cation.

[0078] In a preferred method, the compound of Formula 15 is prepared bycontacting a compound of Formula 3 with a compound of Formula 18:

[0079] wherein M′ is defined herein, under conditions sufficient for theformation of the compound of Formula 15.

[0080] In another preferred method, the compounds of formulas 15 and 17are enantiomerically pure.

[0081] Another specific method of this embodiment is a method ofpreparing omeprazole, or a derivative, prodrug, salt, solvate,clathrate, or stereomerically pure form thereof, which comprisescontacting a compound of Formula 19:

[0082] wherein R₁, R₂, R_(1′), R_(2′), and Prot are defined herein, witha compound of Formula 20:

[0083] wherein M is defined herein, under conditions suitable for theformation of a compound of Formula 21:

[0084] and optionally contacting the compound of Formula 21 with areagent capable of replacing Prot with a hydrogen atom or a cation.

[0085] In a preferred method, the compound of Formula 19 is prepared bycontacting a compound of Formula 3 with a compound of Formula 22:

[0086] wherein M′ is defined herein, under conditions sufficient for theformation of the compound of Formula 19.

[0087] In another preferred method, the compounds of formulas 19 and 21are enantiomerically pure.

[0088] Still another specific method of this embodiment is a method ofpreparing rabeprazole, or a derivative, prodrug, salt, solvate,clathrate, or stereomerically pure form thereof, which comprisescontacting a compound of Formula 15:

[0089] wherein R₁, R₂, R_(1′), R_(2′), and Prot are defined herein, witha compound of Formula 23:

[0090] wherein M is defined herein, under conditions suitable for theformation of a compound of Formula 24:

[0091] and optionally contacting the compound of Formula 24 with areagent capable of replacing Prot with a hydrogen atom or a cation.

[0092] In a preferred method, the compound of Formula 15 is prepared bycontacting a compound of Formula 3 with a compound of Formula 18:

[0093] wherein M′ is defined herein, under conditions sufficient for theformation of the compound of Formula 23.

[0094] In another preferred method, the compounds of formulas 23 and 25are enantiomerically pure.

[0095] A second embodiment of the invention encompasses variouscompounds that are particularly useful for the preparation ofsulfinamides and sulfoxides. For example, the invention encompassescompounds of Formula 7:

[0096] and salts, solvates, clathrates, and stereomerically pure formsthereof, wherein R₃ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, or —NR₄R₅, wherein R₄and R₅ together with the nitrogen atom to which they are attached form aheterocycle or each of R₄ and R₅ is independently hydrogen, isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle; each R₁₀ is independentlysubstituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, substituted or unsubstitutedether, substituted or unsubstituted sulfide, a primary, secondary, ortertiary amine, a heterocycle, or a halogen atom; n is an integer of 1to 4; and m is an integer of 0 to 4.

[0097] In preferred compounds of Formula 7, R₃ is a substituted orunsubstituted lower alkyl, substituted or unsubstituted aralkyl (e.g.,halogenated phenyl, 3-methylphenyl, 2-methylphenyl, 2-mesityl, tolyl,4-(tert-butyl)phenyl, or 2,4,6-triisopropylphenyl), or aryl (e.g.,phenyl and biphenyl). In more preferred compounds, R₃ is 2-mesityl ortolyl.

[0098] In other preferred compounds of Formula 7, each R₁₀ isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, or substituted or unsubstituted aryl. In morepreferred compounds of Formula 7, each R₁₀ is independently alkyl,aralkyl, or aryl.

[0099] In preferred compounds of Formula 7, n is 1 and m is 0, 1, or 2.

[0100] Preferred compounds of Formula 7 are stereomerically pure.

[0101] The invention further encompasses compounds of Formula 25:

[0102] and salts, solvates, clathrates, and stereomerically pure formsthereof, wherein R₁ and R₂ together form a cyclic structure (e.g.,substituted or unsubstituted heterocycle or aryl) or each of R₁ and R₂is independently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, or substitutedor unsubstituted heterocycle; R₃ is substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, or —NR₄R₅, wherein R₄and R₅ together with the nitrogen atom to which they are attached form aheterocycle or each of R₄ and R₄ is independently hydrogen, substitutedor unsubstituted alkyl, substituted or unsubstituted aralkyl,substituted or unsubstituted aryl, substituted or unsubstituted ether,substituted or unsubstituted sulfide, or substituted or unsubstitutedheterocycle; each R₁₁ is independently substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, a primary, secondary, or tertiary amine, aheterocycle, or a halogen atom; R₁₂ is substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, or substituted or unsubstituted heterocycle, oris a sulfoxide; and r is an integer from 0 to 4.

[0103] In preferred compounds of Formula 25, n is 1, m is 0, 1, or 2,and r is 2 or 3.

[0104] In additional preferred compounds of Formula 25, R₁ is phenyl orlower alkyl. In a particular compound, R₁ is methyl.

[0105] In additional preferred compounds of Formula 25, R₂ is phenyl orlower alkyl. In a particular compound, R₂ is phenyl.

[0106] In additional preferred compounds of Formula 25, R₃ is asubstituted or unsubstituted lower alkyl, substituted or unsubstitutedaralkyl (e.g., halogenated phenyl, 3-methylphenyl, 4-methylphenyl,1,3,5-trimethylphenyl, (tert-butyl)phenyl, 2-mesityl, tolyl, or1,3,5-triisopropylphenyl), or aryl (e.g., phenyl and biphenyl). In aparticular compound, R₃ is 2-mesityl or tolyl.

[0107] Specific preferred compounds of Formula 25 are those of Formula26:

[0108] and salts, solvates, clathrates, and stereomerically pure formsthereof, wherein each R₁₁ is independently substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, a primary, secondary, or tertiary amine, aheterocycle, or a halogen atom; R₁₂ is substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, or substituted or unsubstituted heterocycle, oris a sulfoxide; and r is an integer from 0 to 4.

[0109] In preferred compounds of Formula 26, R₁₂ is a protecting group.

[0110] In preferred compounds of Formula 26, each R₁₁ is independentlysubstituted or unsubstituted alkyl or substituted or unsubstitutedether.

[0111] In preferred compounds of Formula 26, n is 1, m is 0, 1, or 2,and r is 2 or 3.

[0112] The invention further encompasses compounds of Formula 9:

[0113] and salts, solvates, clathrates, and stereomerically pure formsthereof, wherein R₃ is substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted aryl, substitutedor unsubstituted ether, substituted or unsubstituted sulfide,substituted or unsubstituted heterocycle, polymer bound alkyl or aryl,or —NR₄R₅, wherein R₄ and R₅ together with the nitrogen atom to whichthey are attached form a heterocycle or each of R₄ and R₅ isindependently hydrogen, substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted aryl, substitutedor unsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle.

[0114] In preferred compounds of Formula 9, R₃ is a substituted orunsubstituted lower alkyl, substituted or unsubstituted aralkyl (e.g.,halogenated phenyl, 3-methylphenyl, 2-methylphenyl, 2-mesityl, tolyl,4-(tert-butyl)phenyl, or 2,4,6-triisopropylphenyl), or aryl (e.g.,phenyl and biphenyl). In more preferred compounds, R₃ is 2-mesityl ortolyl.

[0115] Preferred compounds of Formula 9 are stereomerically pure.

[0116] The invention further encompasses compounds of Formula 10:

[0117] and salts, solvates, clathrates, and stereomerically pure formsthereof, wherein R₃ is substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted aryl, substitutedor unsubstituted ether, substituted or unsubstituted sulfide,substituted or unsubstituted heterocycle, polymer bound alkyl or aryl,or —NR₄R₅, wherein R₄ and R₅ together with the nitrogen atom to whichthey are attached form a heterocycle or each of R₄ and R₅ isindependently hydrogen, substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted aryl, substitutedor unsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle; each R₁₀ is independentlysubstituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, a primary, secondary, ortertiary amine, or a halogen atom; n is an integer of 1 to 4; and m isan integer of 0 to 4.

[0118] In preferred compounds of Formula 10, R₃ is a substituted orunsubstituted lower alkyl, substituted or unsubstituted aralkyl (e.g.,halogenated phenyl, 3-methylphenyl, 2-methylphenyl, 2-mesityl, tolyl,4-(tert-butyl)phenyl, or 2,4,6-triisopropylphenyl), or aryl (e.g.,phenyl and biphenyl). In more preferred compounds, R₃ is 2-mesityl ortolyl.

[0119] In other preferred compounds of Formula 10, n is 1 and m is 0, 1,or 2.

[0120] Preferred compounds of Formula 10 are stereomerically pure.

[0121] Also encompassed by the invention are compounds of Formula 56:

[0122] and salts, solvates, clathrates, and stereomerically pure formsthereof, wherein R₃ is substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted aryl, substitutedor unsubstituted ether, substituted or unsubstituted sulfide,substituted or unsubstituted heterocycle, polymer bound alkyl or aryl,or —NR₄R₅, wherein R₄ and R₅ together with the nitrogen atom to whichthey are attached form a heterocycle or each of R₄ and R₅ isindependently hydrogen, substituted or unsubstituted alkyl, substitutedor unsubstituted aralkyl, substituted or unsubstituted aryl, substitutedor unsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle.

[0123] In preferred compounds of Formula 56, R₃ is a substituted orunsubstituted lower alkyl, substituted or unsubstituted aralkyl (e.g.,halogenated phenyl, 3-methylphenyl, 2-methylphenyl, 2-mesityl, tolyl,4-(tert-butyl)phenyl, or 2,4,6-triisopropylphenyl), or aryl (e.g.,phenyl and biphenyl). In more preferred compounds, R₃ is 2-mesityl ortolyl.

[0124] Preferred compounds of Formula 56 are stereomerically pure.

4.1. Preparation of Sulfinamides and Sulfoxides

[0125] In general, sulfinamides and sulfoxides are prepared according tothis invention by contacting a compound of Formula 1:

[0126] wherein R₁, R_(1′), R₂, R_(2′), R₃, and X are defined herein,with a reagent that will cleave the sulfur-oxygen bond to provide acompound of Formula 2:

[0127] In preferred methods of the invention, the compounds of formulas1 and 2 are stereomerically pure.

[0128] A particular method of the invention is shown below in Scheme II:

[0129] As shown in Scheme II, a compound of Formula 27 is contacted witha compound of the formula HalSO₂R₃, wherein Hal is halogen and R₁, R₂,and R₃ are defined herein, under conditions suitable for the formationof a compound of Formula 28. Examples of HalSO₂R₃ include, but are notlimited to, p-toluenesulfonyl chloride and mesitylsulfonyl chloride. Asthose of skill in the art will recognize, the particular conditionssufficient for this reaction to occur will depend on the specificcompounds being reacted. Suitable conditions will be readily apparent tothe skilled chemist. In one example, triethylamine is used with asolvent such as, but not limited to, methylene chloride. The compound ofFormula 28 is then contacted with a reagent capable of forming afive-membered ring to provide compound 3. One example of such a reagentis SOCl₂ with a base in a suitable solvent. Examples of bases include,but are not limited to, trialkylamines (e.g., triethylamine), pyridine,imidazole, quinoline, and derivatives thereof. Examples of suitablesolvents include, but are not limited to, THF, methyl-THF, CH₂Cl₂,ClCH₂CH₂Cl, toluene, chlorobenzene, dichlorobenzene, dioxanes, MTBE/THF,DME, and other solvent mixtures. Another example of a reagent that canbe used to form the compound of Formula 3 is 2,4,6-collidine or asubstituted pyridine or pyridine analogue in a solvent such as, but notlimited to, THF.

[0130] The effects of various reagents and reaction conditions on theformation and stereochemistry of specific compounds of Formula 3 shownbelow, are provided in Table 1: TABLE 1 (endo)

(exo)

R₁₀′ and Endo:Exo (solvent at −45° C. R₃ R₁₀″ n Base unless otherwiseindicated) 4-methylphenyl H 1 Triethylamine 75:25 (THF) ″ ″ 1Triethylamine 62:38 (THF/CH₂Cl₂ 1:1) ″ ″ 1 Triethylamine 87:13 (CH₃CN) ″″ 1 Triethylamine 73:27 (EtOAc) ″ ″ 1 Imidazole 70:30 (THF) ″ ″ 11-Methylimidazole 75:25 (THF) ″ ″ 1 Pyridine 75:25 (THF) ″ ″ 12,6-Lutidine 85:15 (THF) ″ ″ 1 2,4,6-Collidine 91:9 (THF) ″ ″ 12,6-Di-t- 3:97 (THF) Butylpyridine ″ ″ 1 4-Me-2,6-t-Bu- 20:80 (THF)(−20° C.) pyridine ″ ″ 1 4-t-Butylpyridiene 84.3:15.7 (THF) ″ ″ 1 2,6-15.8:84.2 (CH₂Cl₂, 0° C.) Dimethoxypyridine ″ ″ 1 Quinaldine 87:13 (THF)″ ″ 1 Lepidine 88:12 (THF) ″ CH₃ 1 Pyridine 97:3 (THF) ″ H 2 Pyridine97:3 (THF) ″ ″ 1 4-Picoline 78:22 (THF) 2-mesityl H 1 Triethylamine85:15 (THF) ″ ″ 1 Triisopropylamine 66.7:33.3 (THF) ″ ″ 1 Diethylaniline2:98 (CH₂Cl₂, −15° C.) ″ ″ 1 Diethylaniline 37:63 (THF, −20° C.) ″ ″ 1Triphenyamine No reaction ″ ″ 1 Imidazole 82:18 (THF) ″ ″ 12-Methylimidazole 85.7:14.3 (THF) ″ ″ 1 2-Ethylimidazole 66:33 ″ ″ 1Pyridine 90:10 (THF) ″ ″ 1 2-Phenylpyridine 83:17 (THF) ″ ″ 12,4,6-Collidine 93:7 (THF) ″ ″ 1 2,6- 2:98 (CH₂Cl₂, −15° C.)Dimethoxypyridine ″ ″ 1 2,6- 75:25 (THF, −45° C. - r.t)Dimethoxypyridine ″ ″ 1 Lepidine 94:6 (THF) 2,4,6-triisopropyl H 1Triethylamine 87:13 (THF) phenyl ″ ″ 1 2,4,6-Collidine 95:5 (THF)4-t-butylphenyl H 1 Triethylamine 80:20 (THF) ″ ″ 1 Triethylamine 40:60(CH₂Cl₂) 4-methylphenyl CH₃ 1 Triethylamine 85.7:14.3 (CH₂Cl₂)

[0131] As shown in Scheme II, the ring of compound 3 is selectivelyopened by contacting it with an organometallic reagent to provide acompound of Formula 1. Examples of organometallic reagents include, butare not limited to, those of the formula M′X, wherein M′ of the formulaM′X is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu or is of the formulaCdZ′, BaZ′, MgZ′, ZnZ′, AlZ′₂, MnZ′, InZ′, CuZ′, Ti(OR₁)₃Z′, or Ti(OR₁)₄wherein Z′ is Cl, Br, I, aryl, aralkyl, or heterocycle, wherein R, isdefined herein.

[0132] The sulfur-oxygen bond of the compound of Formula 1 is thencleaved by contacting it with a compound of formula MY to provide thedesired sulfinamide or sulfoxide of Formula 2. MY can be the same ordifferent from MZ: M is a metal such as Al, Ba, Li, Na, K, Mg, Mn, Zn,Cd, In, Cu or is of the formula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ, orCuZ, Ti(OR₁)₃Z, or Ti(OR₁)₄ wherein Z is Cl, Br, I, aryl, aralkyl, orheterocycle, wherein R, is defined herein.

[0133] Depending on the actual compound of formula MY, this finalreaction of Scheme II can provide a variety of different sulfoxides andsulfinamides, and stereomerically pure sulfoxides and sulfinamides inparticular. For example, when MY is NH₂Li/NH₃, this method can be usedto provide stereomerically pure alkyl (e.g., tert-butyl), aryl (e.g.,tolyl), heteroalkyl (e.g., tert-butyl amino), heterocyclic (e.g.,tetrahydrofuryl , or heteroaryl (e.g., pyridyl) sulfinamide.

[0134] Specific methods of the invention, which can be used to prepareenantiomerically pure pantoprazole, lansoprazole, omeprazole, andrabeprazole, and pharmaceutically acceptable salts, solvates,clathrates, hydrates, prodrugs, and stereomerically pure forms thereof,are represented below in schemes III-VI, respectively. In each scheme,the stereochemistry of the compound of Formula 3 is different in orderto emphasize that the stereochemistry of the final product can be variedby simply altering the corresponding stereochemistry of the startingmaterial. As with all schemes disclosed herein, those shown below areprovided by way of illustration, and are not to be construed as limitingthe scope of the invention.

[0135] In each of schemes III-VI, M and M′ are as defined herein, andProt is a protecting group. Suitable protecting groups are known in theart and include, but are not limited to, —CH₂OCH₃, —CH₂OCH₂OCH₃, alkylsulfonyl, and aryl sulfonyl.

[0136] The reagents used in each of these schemes are commerciallyavailable or readily prepared. For example, the benzimidazole metalconjugates used in the first step of each of schemes III-VI (i.e.,compounds 14, 18, 22 and 18) can be prepared by methods known in theart. See, e.g., Abarbri, M., et al., Tetrahedron Lett. (1999)40:7449-7453 and Abarbri, M., et al., J. Org. Chem. (2000) 65:4618-4634.The synthesis of protected benzimidazoles is also well known. See, e.g.,Sih, J. C. et al., J. Med. Chem. (1991) 34:1049-1062 and Singh, M. P.,et al., Heterocycles (1993) 36:971-985. The pyridinyl metal conjugatesused in the second step of each of the schemes (i.e., compounds 12, 16,20, and 23) are also readily prepared using well-known methods. See,e.g., Baldenius, K. -U. and Kagan, H. B., Tetrahedron: Asym. (1990)1:597-610.

5. EXAMPLES

[0137] Certain embodiments of the invention are illustrated by thefollowing non-limiting examples.

5.1. Example 1 Asymmetric Synthesis of a Sulfinamide Via1,2,3-Oxathiazolidine-S-Oxide

[0138] Examples of the general approach shown in Scheme II are describedbelow, and can be understood with reference to Schemes VII-XII:

[0139] Preparation of(1R,2S)-1-amino-2-indanol-N-2,4,6-mesitylsulfonamide (31):

[0140] To a 2 L mL three neck round-bottomed flask equipped with anoverhead stirrer and temperature probe, was charged NaHCO₃ (42.2 g, 502mmol), followed by 200 mL of water and the mixture was stirred for 15min. EtOAc (500 mL), THF (100 mL), and aminoindanol (30) (50 g, 336mmol) were added and the slurry was mixed for 5 minutes.2-Mesitylenesulfonyl chloride (70.4 g, 322 mmol) was added in oneportion, the reaction mixture was stirred vigorously for 5-6 hours, andthe reaction was monitored by TLC for the disappearance of2-mesitylenesulfonyl chloride. Stirring was stopped and the phases wereallowed to separate. The organic phase was washed with water (200 mL),1.5 M HCl (75 mL) and water (200 mL). Evaporation of the organic solventto dryness provided a solid product which was treated with heptane (400mL) and the mixture was stirred for 2 hours. The resulting slurry wasfiltered and the wet cake dried under reduced pressure to give 104 g(93%) of the title product. ¹H NMR(300 MHz, CDCl₃): δ 2.30 (s, 3H), 2.68(s, 6H), 2.81-3.04 (m, 3H), 4.22-4.32 (m, 1H), 4.48-4.58 (m, 1H),5.58-5.61 (d, J=9.5 Hz, 1H), 6.95-7.24 (m, 6H). ¹³C NMR (CDCl₃): δ 21.3,23.3, 39.6, 61.3, 73.2, 124.9, 125.6, 127.4, 128.7, 132.3, 134.1, 139.7,139.8, 140.0, and 142.8. Alal. Calcd for C₁₈H₂₁NO₃S: C, 65.23; H, 6.39;N, 4.23; 0, 14.48; 5, 9.68. Found: C, 65.36; H, 6.40; N, 4.08; S, 9.70.

[0141] Preparation of (2R,4R,5S)-3-(2,4,6-mesitylsulfonyl-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopentaralindene 2-oxide(32) from (1R,2S)-aminoindanol mesitylene sulfonamide (31):

[0142] To a 1 L three-necked flask equipped with a mechanical stirrer,an argon inlet, a thermometer probe and rubber septum, was charged(1R,2S)-aminoindanol mesitylene sulfonamide (31 g, 93.7 mmol), THF (50mL) and the reaction mixture was cooled to −45° C. Thionyl chloride(15.2 g, 128 mmol) was added slowly via syringe in one portion, followedby slow addition of collidine (32 g, 264 mmol) in THF (250 mL) for 6hours. The reaction was quenched with aqueous NaHCO₃ (100 mL), dilutedwith EtOAc (100 mL) and warmed to room temperature. The organic layerwas washed with brine (100 mL), dried with Na₂SO₄and concentrated todryness. The residue was added heptane (150 mL), stirred for 2 hours,and filtered to give a white or off white solid product with 85% de.Crystallization from EtOAc/heptane provided a white solid product. Themother liquor was concentrated, and a second crop of crystals wasobtained. This process was repeated two times to give a total yield of28 g (78%) of(2R,4R,5S)-3-(2,4,6-mesitylsulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (32) with >99% de.

[0143] Preparation of(2S,4S,5R)-3-(2,4,6-mesitylsulfonyl-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (36) from (1S,2R)-1-amino-2-indanol-N-2,4,6-mesitylsulfonamide(35):

[0144] The same procedure described above was used to provide theproduct with 76% yield and >99% de. ¹H NMR (CDCl₃): δ 2.41 (s, 3H), 2.77(s, 6H), 3.40-3.66 (m, 2H), 5.57 (d, J=6.4 Hz, 1H), 5.86-5.91 (m, 1H),6.63 (d, J=8.1 Hz, 1H), 7.08-7.34 (m, 5H). ¹³C NMR (CDCl₃): δ 21.5,23.4, 39.6, 66.6, 96.0, 125.0, 125.8, 128.1, 129.8, 132.8, 138.8, 141.2,145.1. Anal. C₁₈H₁₉NO₄S₂, Cal: C, 57.27; H, 5.07; N, 3.71; S, 16.99.Found: C, 57.45; H, 5.14; N, 3.76; S, 16.93.

[0145] Preparation of aminoindanol 4-toluene sulfonamide(1R,2R,3S)-1,2,3-oxathiazolidine-S-oxide (39) from(1R,2S)-1-amino-2-indanol-N-4-toluenesulfonamide (38) or aminoindanol4-toluene sulfonamide (1S,2S,3R)-1,2,3-oxathiazolidine-S-oxide (42) from(1S,2R)-1-amino-2-indanol-N-4-toluenesulfonamide (41):

[0146] The same procedure described above was used to provide the titlecompound quantitatively with 82% de. Crystallization from heptane/EtOAcfurnished the diastereomeric pure product with >99% de (minordiastereomere not detected) and 65% yield. ¹H NMR (CDCl₃): δ 2.51 (s,3H), 3.32-3.62 (m, 2H), 5.38-5.52 (m, 2H), 7.81-7.89 (m, 6H), 7.81-7.89(m, 2H). ¹³C NMR (CDCl₃): δ 22.0, 39.7, 67.1,93.3, 125.6, 126.0, 127.8,128.1, 130.0, 130.6, 135.9, 138.2, 138.6, 145.6. Anal: C₁₆H₁₅N₄S₂, Cal:C, 55.00; H, 4.33; N, 4.01; S, 18.35. Found: C 55.09; H, 4.37; N, 3.92;S, 18.39.

[0147] Prepartion of(2S,4R,5S)-3-(4-toluenesulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopentaralindene2-oxide (44) from (1R,2S)-1-amino-2-indanol-N-4-toluenesulfonamide (38):

[0148] A 250 mL three-necked flask equipped with a mechanical stirrer,an argon inlet, a thermometer probe and rubber septum, was charged(1R,2S)-1-amino-2-indanol-N-4-toluenesulfonamide (10.0 g, 33.0 mmol),THF (30 mL) and the reaction mixture was cooled to −45° C. Thionylchloride (5.9 g, 49.6 mmol) was added slowly via syringe in one portion,followed by slow addition of 2,6-di-t-butyl pyridine (15.8 g, 80.0 mmol)in THF (100 mL) for 1-2 hours, and the reaction mixture was allowed towarm to room temperature with stirring. After 6-8 hours, as monitored byTLC for disappearance of starting material, the reaction mixture wascooled to −5° C. and quenched with aqueous NaHCO₃ (40 mL), diluted withEtOAc (100 mL) and warmed to room temperature. The organic layer waswashed with brine (100 mL) and concentrated to dryness. The residue wasadded heptane (100 mL), stirred for 2 hours, and filtered to give awhite or off white solid product (11 .0 g, 95.5%) with >97% de (thecrude product was used directly in the next step). Crystallization fromEtOAc/heptane furnished diastereomeric pure product (>99% de, minordiastereomer not detected).

[0149] Preparation of(2R,4S,5R)-3-(4-toluenesulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (46) from (1S,2R)-1-amino-2-indanol-N-4-toluenesulfonamide (41):

[0150] The same procedure described above was used to provide the titleproduct with same result. ¹H NMR (CDCl₃): δ 2.46 (s, 3H), 3.31 (s, 2H),5.02-5.04 (d, J=5.0 Hz, 1H), 5.77-5.82 (m, 1H), 7.22-7.42 (m, 5H),7.96-8.04 (m, 3H). ¹³C NMR(CDCl₃): δ 22.0, 36.2, 65.1, 90.6, 125.2,127.0, 128.9, 129.8, 130.2, 135.5, 137.9, 139.2, 145.5. Anal C₁₆H₁₅NO₄S₂Cal: C, 55.0; H, 4.33; N, 4.01; S, 18.35. Found: C, 55.11; H, 4.35; N,4.00; S, 18.4.

[0151] Preparation of (S)-2-Methyl-2-propylsulfinic Acid(1R,2S)-1-(2,4,6-mesitylsulfonylamino)-indan-2-yl Ester (33) from(2R,4R,5S)-3-(2,4,6-mesitylsulfonyl-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopentaralindene 2-oxide(32):

[0152] In a 100 mL two-necked, round-bottomed flask equipped with amagnetic stir bar, rubber septum, and argon inlet was placed(2R,4R,5S)-3-(2,4,6-mesitylsulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (32) (2.2 g, 5.8 mmol) dissolved in THF (20 mL) and the mixturewas cooled to −10° C. A solution of t-butyl magnesium chloride (10.8 mL,1.0 M) in THF was added dropwise via syringe for 1 hour and the reactionwas allowed to warm to room temperature with stirring. After 2 hours, asmonitored by TLC for the disappearance of the starting material, thereaction mixture was cooled to 0° C. quenched with aqueous NaHCO₃ (10mL), and diluted with EtOAc (20 mL). The aqueous phase was extractedwith EtOAc (10 mL). The combined organic phases were washed with brine(20 mL), dried with Na₂SO₄ and concentrated to afford a crystallineproduct (2.45 g, 96.5%) with >99% de (minor diastereomer not detected).

[0153] Preparation of (R)-2-Methyl-2-propylsulfinic acid(1S,2R)-1-(2,4,6-mesitylsulfonylamino)-indan-2-yl ester (37) from(2S,4S,5R)-3-(2,4,6-mesitylsulfonyl-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene 2-oxide(36):

[0154] The same procedure described above was used. The result provided95% yield and >99% de. ¹H NMR (CDCl₃): δ 1.07 (s, 9H), 2.32 (s, 3H),2.71 (s, 6H), 3.06 (s, 2H), 4.75-4.85 (m, 2H), 5.64 (d, J=9.3 Hz, 1H),6.99 (s, 1H), 7.17-7.28 (m, 5H). ¹³C NMR (CDCl₃): δ 21.1, 21.8, 37.8,58.1, 60.5, 82.7, 124.8, 124.9, 127.8, 128.5, 132.3, 134.6, 137.8,139.6, 140.3, 142.6. Anal. C₂₂H₂₉NO₄S₂: Cal. C, 60.66; H, 6.71; N, 3.22;S, 14.72. Found: C, 60.75; H, 6.72; N, 3.15; S, 14.65.

[0155] Preparation of (S)-2-Methyl-2-propylsulfinic Acid(1R,2S)-1-(4-toluenesulfonylamino)-indan-2-yl Ester (40) from(2R,4R,5S)-3-(4-toluenesulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (39) and (R)-tert-butyl (1S,2R) aminoindanol 4-toluenesulfonamide sulfinate (43) from aminoindanol 4-toluene Sulfonamide(1S,2S,3R)-1,2,3-oxathiazolidine-S-oxide (42):

[0156] The same procedure described above was used to provide the titleproduct with 96% yield and >99% de. ¹H NMR (CDCl₃): δ 1.12 (s, 9H), 2.48(s, 3H), 2.95-3.14 (m, 2H), 4.64-4.70 (m, 1H), 4.76-4.84 (m, 1H), 5.76(d, 9.2 Hz, 1H), 7.16-7.50 (m, 6H), 7.94-7.97 (m, 2H). ¹³C NMR (CDCl₃):δ 21.7, 38.0, 58.2, 60.6, 83.1, 124.9, 124.995, 127.8, 128.6, 130.0,137.5, 140.1, 143.8. Anal: C₂₀H₂₅NO₄S₂. Cal: C, 58.94; H, 6.18; N, 3.44;S, 15.74. Found: C, 59.10; H, 6.22; N, 3.35; S, 15.79.

[0157] Preparation of (R)-2-Methyl-2-propylsulfinic Acid(1R,2S)-1-(4-toluenesulfonylamino)-indan-2-yl Ester (45) from(2S,4R,5S)-3-(4-toluenesulfonl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (44):

[0158] In a 100 mL two-necked, round-bottomed flask equipped with amagnetic stir bar, rubber septum, and argon inlet wasplaced(2S,4R,5S)-3-(4-toluenesulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (4.5 g, 12.9 mmol) dissolved in THF (30 mL) and the mixture wascooled to 0° C. A solution of t-butyl magnesium chloride (25 mL, 1.0 M)in THF was added dropwise via syringe for 30 minutes with stirring.After 3-4 hours, as monitored by TLC for the disappearance of thestarting material, the reaction was quenched with aqueous NaHCO₃ (20mL), and diluted with EtOAc (50 mL). The aqueous phase was extractedwith EtOAc (20 mL) and the combined organic phases were washed withbrine (40 mL), dried with Na₂SO₄ and concentrated to afford acrystalline product (5.0 g, 95%) with >99% de (minor diastereomer notdetected). ¹H NMR (CDCl₃): δ 1.12 (s, 9H), 2.45 (s, 3H), 3.08-3.26 (m,2H), 4.84-4.88 (m, 1H), 4.94-4.97 (m, 1H), 5.32 (d, J=10.1 Hz),7.06-7.35 (m, 6H), 7.83-7.86 (m, 2H). ¹³C NMR (CDCl₃): δ 21.7, 21.9,38.6, 58.3, 60.8, 81.8, 124.1, 125.2, 127.3, 127.5, 128.9, 130.0, 138.1,138.5, 139.2, 143.9.

[0159] Preparation of (S)-t-butyl (1R,2S) Aminoindanol MesityleneSulfonamide Sulfinate (33) (One Pot Procedure):

[0160] A 50 mL three-necked flask equipped with a mechanical stirrer, anargon inlet, a thermometer probe and rubber septum, was charged(1R,2S)-aminoindanol mesitylene sulfonamide (1.22 g, 3.2 mmol), THF (3mL) and the reaction mixture was cooled to −45° C. Thionyl chloride(0.58 g, 4.9 mmol) was added slowly via syringe in one portion, followedby slow addition of collidine (1.19 g, 9.8 mmol) in THF (10 mL) for 3-4hours, and the reaction was monitored by TLC. The reaction mixture waswarmed to −5° C.-10° C. and stirred for 5 min. The collidine-HCl saltwas filtered and the cake washed with THF (4 mL). The filtrate wascooled to −78° C. and tBuMgCl (6.4 mL, 1.0 M) in THF was added slowly.After 4-5 hours, as monitored by TLC for the disappearance of thestarting material, aqueous NaHCO₃ (10 mL) was added to quench thereaction, diluted with EtOAc (15 mL) and the mixture was allowed to warmto room temperature The organic phase was washed with brine, 10% NaCland dried (Na₂SO₄). Removal of the solvent afforded a viscous oil thatwas added EtOAc (3 mL) and heptane (10 mL) and stirred for 30 minutes.The crystalline precipitate formed was filtered and washed with heptaneand dried to afford the title compound (1.2 g, 75%) with >95% de. (Thede was measured by ¹H NMR). ¹H NMR (CDCl₃): δ 1.40 (s, 9H), 2.34 (s,3H), 2.74 (s, 6H), 3.06-3.08 (s, 2H), 4.77-4.90 (m, 2H), 5.65 (d, J=10Hz), 7.02 (s, 1H), 7.27-7.37 (m, 5H). ¹³C NMR (CDCl₃): δ 21.2, 21.8,37.8, 58.1, 60.5, 82.7, 124.8, 124.9, 127.8, 128.5, 132.3, 134.6, 137.6,139.6, 140.5, 142.6.

[0161] Preparation of (R)-t-butylsulfinamide (8(R): (R)-TBSA) from(S-tert-Butyl (1R,2S)-aminoindanol Mesitylene Sulfonamide Sulfinate(33):

[0162] A 250 mL three-necked round-bottomed flask equipped with amechanical stirrer and an ammonia condenser at about −78° C. was chargedwith 50 mL of liquid ammonia under Ar atmosphere. After the addition ofa few crystals of Fe(NO₃)₃, lithium wire (0.25 g, 35 mmol) was addedportion-wise in a controlled manner and the internal temperature waskept around −45° C. When all the lithium was added and a gray suspensionwas formed, the reaction mixture was cooled to −78° C. and a solution of(S)-t-butyl (1R,2S)-aminoindanol mesitylene sulfonamide sulfinate ester(5 g, 11.5 mmol) in THF (15 mL) was added slowly over a course of 45min. Once the addition was complete, the mixture was stirred foradditional 30-45 min. before NH₄Cl (2.8 g) was added. The cold bath wasremoved, and stirring continued until the mixture reached ambienttemperature. The remaining volatile material was removed under reducedpressure. To the remaining residue was added 5 mL water and stirred.EtOAc (50 mL) was added to the mixture and stirred. After separation ofthe phases, the organic phase was washed with brine (5 mL×2). Afterremoval of the organic solvent, the residue was added water (40 mL) andstirred for 1 hour. The slurry was filtered and the wet cake was washedwith water (10 mL). The aqueous filtrate was then saturated with NaCland extracted with EtOAc (20 mL×3). Removal of the organic solventafforded (R)-t-butylsulfinamide (0.75 g, 70%) with 97% ee. (HPLC,Chiralpak AS column, 90:10 hexane/ethanol; 1.2 mL/min, 222 inn; (R)-TBSAr, =6.6 min.; (S)-TBSA, r_(t)=9.4 min.). ¹H NMR (CDCl₃): δ 1.18 (s, 9H),3.82 (br, s, 2H). ¹³C NMR(CDCU): δ 22.1, 55.3.

[0163] Preparation of (R)-2-Methyl-2-propylsulfinic Acid(1S,2R)-1-(2,4,6-mesitylsulfonylamino)-indan-2-yl Ester (37) or from(R)-2-Methyl-2-propylsulfinic Acid(1R,2S)-1-(4-toluenesulfonylamino)-indan-2-yl ester (45):

[0164] The same procedure described above was used to provide the titleproducts with 98% ee and 73% yield or 98% ee and 72% yield,respectively.

5.2. Example 2 Sulfinamide Synthesis Via (1S,2R)-1-(N-MesityleneSulfonyl)Amino-1-Phenyl-2-Propanol

[0165] One method of preparing sulfinamides is represented by SchemeXIII, below:

[0166] Preparation of(1S,2R)-N-(2-hydroxy-1-phenyl-propyl)-2.4.6-mesitylsulfonamide (49):

[0167] (1S,2R)-1-amino-1-phenyl-2-propanol (48) (2.0 g, 10.6 mmol) wascharged into a 100 mL three neck round-bottomed flask equipped with anoverhead stirrer and temperature probe, followed by methylene chloride(20 mL) and the mixture was cooled to 0° C. and stirred for 15 minutes.2-Mesitylenesulfonyl chloride (2.2 g, 10.1 mmol) was added in oneportion and the slurry was mixed for 5 minutes. Triethylamine (2.7 g,26.7 mmol) was added in 2 hours with stirring and the reaction wasmonitored by TLC for the disappearance of 2-mesitylenesulfonyl chloride.The reaction was quenched with saturated aqueous NaHCO₃ (20 mL) anddiluted with EtOAc (20 mL). The organic phase was washed with water (20mL), 1.0 M HCl (10 mL), water (20 mL) and dried over NaSO₄. Evaporationof the organic solvent to dryness provided the title product in 95%yield (3.3 g). ¹H NMR (CDCl₃): δ 1.02 (d, J=6.35 Hz, 3H), 2.14 (d,J=5.49 Hz, 1H), 2.21 (s, 3H), 2.49 (s, 6H), 4.07-4.11 (m, 1H), 4.15-4.18(m, 1H), 5.70 (d, J=7.21 Hz, 1H), 6.76 (s, 2H), 6.99-7.15 (m, 5H). ¹³CNMR (CDCl₃): δ 19.5, 21.1, 23.1, 63.0, 70.4, 127.9, 128.3, 132.0, 134.3,136.7, 139.0, 142.3. Anal: C18H23NO3S. Cal: C, 64.84; H, 6.95; N, 4.20,S, 9.62. Found: C, 65.19; H, 7.04; N, 4.18; S, 9.71.

[0168] Preparation of(2S,4S,5R)-5-methyl-4-phenyl-3-(2,4,6-mesitylsulfonyl)-[1,2,3]oxathiazolidine2-oxide (50):

[0169] A 50 mL three-necked flask equipped with a mechanical stirrer, anargon inlet, a thermometer probe and rubber septum, was(1S,2R)-N-(2-hydroxy-1-phenyl-propyl)-2,4,6-mesitylsulfonamide (49)(1.89 g, 5.67 mmol), THF (5 mL) and the reaction mixture was cooled to−45° C. Thionyl chloride (1.01 g, 8.50 mmol) was added slowly viasyringe in one portion, followed by slow addition of 2,4,6-collidine(2.10 g, 14.18 mmol) in THF (10 mL) for 2-3 hours, and the reaction wasmonitored by TLC for the disappearance of starting material. Thereaction was quenched with saturated aqueous NaHCO₃ (10 mL), dilutedwith EtOAc (20 mL) and the mixture was warmed to room temperature. Theorganic layer was washed with brine (10 mL) and concentrated to dryness.The residue was added heptane (20 mL), stirred for 2 hours, and filteredto give a white or off white solid product with 94% de. Crystallizationfrom MTBE furnished diastereomeric pure product (1.9 g, 88.5%) with >99%de (minor diastereomer not detected by NMR). ¹H NMR (CDCl₃): δ 1.14 (d,J=6.59 Hz, 3H), 2.16 (s, 3H), 2.52 (s, 6H). 4.87 (d, J=6.72 Hz, 1H),5.16 (p, J=6.59, 1H), 6.70 (s, 2H), 7.08-7.13 (m, 5H). ¹³C NMR (CDCl₃):δ 18.07, 21.06, 23.00, 65.34, 87.64, 128.20, 128.28, 131.51, 132.11,132.93. 140.59, 144.23. Anal: C18H21NO4S2. Cal: C, 56.97; H, 5.58; N,3.69; S,16.90. Found: C, 57.16; H, 5.62; N, 3.62; S,16.94.

[0170] (S)-2-Methyl-2-propylsulfinic Acid(1S,2R)-1-methyl-2-phenyl-2-(2,4,6-mesitylsulfonylamino)-ethyl ester(51):

[0171] In a 50 mL two-necked, round-bottomed flask equipped with amagnetic stir bar, rubber septum, and argon inlet was placed(2S,4S,5R)-5-methyl-4-phenyl-3-(2,4,6-mesitylsulfonyl)-[1,2,3]oxathiazolidine2-oxide (50) (0.58 g, 1.53 mmol) dissolved in THF (1.0 mL) and themixture was cooled to −78° C. A solution of t-butyl magnesium chloride(3.1 mL, 1.0 M) in THF was added dropwise via syringe for 30 minuteswith stirring. After 1-2 hours, as monitored by TLC for thedisappearance of the starting material, the reaction was quenched withsaturated aqueous NaHCO₃ (5 mL), and diluted with EtOAc (5 mL). Theaqueous phase was extracted with EtOAc (4 mL) and the combined organicphases were washed with brine (5 mL), dried with (Na₂SO₄) andconcentrated to afford a crystalline product (0.65 g. 97%) with >99% de(minor diasteriomer not detected). ¹H NMR (CDCl₃): δ 1.080 (d, J=6.47Hz, 3H), 1.1749 (s, 9H), 2.163 (s, 3H), 2.485 (s, 6H), 4.394 (dd,J1=8.98 Hz, J2=2.32 Hz, 1H), 4.675 (dq, J1=2.32 Hz, J2=6.53 Hz, 1H),6.61-6.67 (m, 2H), 6.96-7.09 (m, 5H). ¹³C NMR (CDCl₃): δ 19.10, 20.90,21.80, 22.98, 57.85, 61.10, 81.86, 127.58, 128.80, 131.61, 134.98,135.10, 138.50, 141.55.

[0172] Preparation of (S)-t-butylsulfinamide ((S)8) from(S)-2-Methyl-2-propylsulfinic Acid(1S,2R)-1-methyl-2-phenyl-2-(2,4,6-mesitylsulfonylamino)-ethyl Ester(51):

[0173] A 50 mL three-necked round-bottomed flask equipped with amagnetic stir bar and an ammonia condenser was charged with 30 mL ofliquid ammonia under Ar atmosphere. After the addition of a few crystalsof Fe(NO₃)₃, lithium wire (0.05 g, 7.1 mmol) was added in a controlledmanner and the internal temperature was kept around −45° C. When all thelithium was added and a gray suspension was formed, the reaction mixturewas cooled to −78° C. and a solution of (S)-2-methyl-2-propylsulfinicacid (1S,2R)-1-methyl-2-phenyl-2-(2,4,6-mesitylsulfonylamino)-ethylester (51) (0.45 g, 1.03 mmol) in THF (1 mL) was added slowly over acourse of 20 minutes. Once the addition was complete, the mixture waswarmed to −45° C. and stirred for 1 hour, followed by addition of NH₄Cl(0.5 g). The cold bath was removed, and stirring continued until themixture reached ambient temperature. The remaining volatile material wasremoved under reduced pressure. To the remaining residue was added 2 mLwater and stirred. EtOAc (5 mL) was added to the mixture and stirred.After separation of the phases, the organic phase was washed with brine(2 mL×2). After removal of the organic solvent, the residue was purifiedby chromatography eluted with EtOAc to afforded (S)-t-butylsulfinamide(0.125 g, 99%) with 99% ee. (HPLC, Chiralpak AS column, 90:10hexane/ethanol; 1.2 mL/min, 222 nm; (R)-TBSA r_(t)=6.6 min; (S)-TBSA,r_(t)=9.4 min.). ¹H NMR (CDCl₃): δ 1.18 (s, 9H), 3.82 (br, s, 2H). ¹³CNMR(CDCl₃): δ 22.1, 55.3.

5.3. Example 3 Sulfinamide Synthesis Via (1S,2R)-Norephedrine 4-TolueneSulfonamide

[0174] Another method of preparing sulfinamides is represented by SchemeXIV, below:

[0175] Preparation of(1S,2R)-N-(1-hydroxy-2-methyl-1phenyl-ethyl)-4-toluene sulfonamide (53):

[0176] To a 250 mL three neck round-bottomed flask equipped with anoverhead stirrer and temperature probe, was charged (1S,2R)-norephedrine(10.0 g, 66.1 mmol), followed by tosyl chloride (12.1 g, 63.6 mmol) andthe mixture was cooled to 0° C. and stirred for 15 minutes. Then Et₃Nwas added in 2 hours with stirring and the reaction was monitored byTLC. The reaction was quenched with saturated aqueous NaHCO₃ (50 mL).The organic phase was washed with water (50 mL), 1.0 M HCl (25 mL),water (50 mL) and dried over NaSO₄. Evaporation of the organic solventto dryness provided a oily crude product that was crystallized fromMTBE/hexane to give the title product (18.5 g) with 90% yield.

[0177] (1R,2S)-Norephedrine 4-toluene sulfonamide was prepared byfollowing the same method with 91% yield. ¹H NMR (CDCl₃): δ 0.814 (d,J=6.83 Hz, 3H), 2.40 (s, 3H), 3.116 (d, J=4.76 Hz, 1H), 3.42-3.52 (m,1H), 4.786-4.812 (m, 1H), 5.138 (d, J=8.67 Hz, 1H), 7.200-7.316 (m, 7H),7.767 (d, J=8.30 Hz, 2H). ¹³C NMR(CDCl₃): δ 14.49, 21.66, 55.16, 75.85,126.19, 127.16, 127.69, 128.41, 129.90, 137.84, 140.48, 143.60.

[0178] Preparation of (2R,4R,5S)-4-methyl-5-phenyl-3-(4-toluenesulfonyl-[1,2,3]oxathiazolidine 2-oxide (54):

[0179] A 100 mL three-necked flask equipped with a magnetic stir bar, anargon inlet, a thermometer probe and rubber septum, was charged(1S,2R)-N-(1-hydroxy-2-methyl-1phenyl-ethyl)-4-toluenesulfonamide (53)(5.2 g, 17.04 mmol), THF (15 mL) and the reaction mixture was cooled to−45° C. Thionyl chloride (3.04 g, 25.5 mmol) was added slowly viasyringe in one portion, followed by slow addition of 2,4,6-collidine(6.2 g, 51.2 mmol) in THF (30 mL) for 2-3 hours, and the reaction wasmonitored by TLC for the disappearance of starting material. Thereaction was quenched by addition of NaHCO₃ (5.0 g) and saturatedaqueous NaHCO₃ (20 mL), diluted with EtOAc (40 mL) and the mixture waswarmed to room temperature. The organic layer was washed with brine (50mL), dried over Na₂SO₄ and concentrated to dryness. The residue wasadded heptane (50 mL), stirred for 1 hour, and filtered to give a whiteor off white solid product (5.6 g, 94%) with 97% de. The product wasused directly in the next step reaction. Diastereomerically purecompound was obtained by crystallization from MTBE.

[0180] (2S,4S,5R)-3-Tosyl-4-methyl-5-phenyl-2-oxo-1,2,3-oxathiazolidinewas prepared by following the same method with 93% yield and 97% de. ¹HNMR (CDCl₃): δ 0.868 (d, J=6.97 Hz, 3H), 2.545 (s, 3H), 4.210 (p, J=6.48Hz, 1H), 5.572 (d, J=5.98 Hz, 1H), 7.284-7.388 (m, 7H), 7.864-7.892 (m,2H). ¹³C NMR (CDCl₃): δ 16.59, 21.48, 57.12, 92.14, 126.39, 127.68,128.86, 129.16, 130.35, 133.41, 136.62, 145.34.

[0181] (R)-2-Methyl-2-propylsulfinic acid(1S,2R)-1-phenyl-2-(4-toluenesulfonylamino)propyl ester (55):

[0182] In a 100 mL two-necked, round-bottomed flask equipped with amagnetic stir bar, rubber septum, and argon inlet was placed(2R,4R,5S)-4-methyl-5-phenyl-3-(4-toluenesulfonyl)-[1,2,3]oxathiazolidine2-oxide (54) (4.5 g, 12.8 mmol) dissolved in THF (30.0 mL) and themixture was cooled to −78° C. A solution of t-butyl magnesium chloride(25 mL, 1.0 M) in THF was added dropwise via syringe for 30 minutes withstirring. After 1-2 hours as monitored by TLC for the disappearance ofthe starting material, the reaction was quenched with aqueous NaHCO₃ (30mL), and diluted with EtOAc (40 mL). The aqueous phase was extractedwith EtOAc (20 mL) and the combined organic phases were washed withbrine (40 mL), dried with (Na₂SO₄) and concentrated to afford acrystalline product (5.2 g, 99%) with 97% de.

[0183] (S)-2-Methyl-2-propylsulfinic acid(1R,2S)-1-phenyl-2-(4-toluenesulfonylamino)propyl ester was prepared byfollowing the same method with 98% yield and 97% de. ¹H NMR (CDCl₃): δ0.981 (d, J=6.84 Hz, 3H), 1.251 (s, 9H), 2.428 (s, 3H), 3.56-3.675 (m,1H), 4.956 (d, J=2.32 Hz, 1H), 5.841 (d, J=9.77 Hz, 1H), 7.073-7.105 (m,2H), 7.270-7.350 (m, 5H), 7.85-7.879 (m, 2H). ¹³C NMR (CDCl₃): δ 14.88,21.67, 21.90, 54.57, 58.34, 84.82, 125.98, 127.31, 128.36, 128.66,129.86, 137.37, 138.48, 143.46.

[0184] Preparation of (R)-t-butylsulfinamide ((R)-TBSA) from(R)-2-Methyl-2-propylsulfinic Acid(1S,2R)-1-phenyl-2-(4-toluenesulfonylamino)-propyl Ester (55):

[0185] A 100 mL three-necked round-bottomed flask equipped with amagnetic stir bar and an ammonia ; condenser was charged with 50 mL ofliquid ammonia under Ar atmosphere. After the addition of a few crystalsof Fe(NO₃)₃, lithium wire (0.3 g, 42.8 mmol) was added in a controlledmanner and the internal temperature was kept around −45° C. When all thelithium was added and a gray suspension was formed, the reaction mixturewas cooled to −78° C. and a solution of (S)-t-butyl (1S,2R)-norephedrinesulfinate (2.6 g, 6.3 mmol) in THF (6 mL) was added slowly over a courseof 40 minutes. Once the addition was complete, as the reaction wasmonitored by TLC for the disappearance of the starting material, themixture was added NH₄Cl (4.0 g). The cold bath was removed, and stirringcontinued until the mixture reached ambient temperature. The remainingvolatile material was removed under reduced pressure. To the remainingresidue was added 5 mL of water and stirred. EtOAc (50 mL) was added tothe mixture and stirred. After separation of the phases, the organicphase was washed with brine (6 mL×2). After removal of the organicsolvent, the residue was purified with chromatography eluted with EtOActo afforded (R)-t-butylsulfinamide (0.65 g, 85%) with 96% ee.

[0186] Preparation of (S)-t-butyl Sulfinamide from(S)-2-Methyl-2-propylsulfinic Acid(1R,2S)-1-phenyl-2-(4-toluenesulfonylamino)-propyl ester:

[0187] The same procedure described above was followed, an furnished thetitle product in 86% yield and 96% ee. (HPLC, Chiralpak AS column, 90:10hexane/ethanol; 1.2 mL/min, 222 nm; (R)-TBSA r_(t)=6.6 min; (S)-TBSA,r_(t)=9.4 min.). ¹H NMR(CDCl₃): δ 1.18 (s, 9H), 3.82 (br, s, 2H). ¹³CNMR (CDCl₃): δ 22.1, 55.3.

5.4. Example 4 Preparation of Enantiomerically Pure Sulfoxides

[0188] Stereomerically pure (e.g., enantiomerically pure) sulfoxides canbe readily prepared using methods of the invention. Specific methods areshown below in schemes XV and XVI:

[0189] The following can be understood with reference to the schemesshown above.

[0190] Preparation of (S)-t-butyl Isobutyl Sulfoxide:

[0191] A THF (40 mL) solution of (S)-tert-butyl (1R,2S)-aminoindanolmesitylene sulfonamide sulfinate (5.8 g) at −5° C. was slowly added toiBuMgBr (10.5 mL, 2M) in ether. After addition, the reaction mixture waswarmed to 10° C., stirred and the reaction was monitored by TLC. Thereaction was quenched by aqueous NH₄Cl, diluted with EtOAc (20 mL) andstirred. The organic phased was washed with brine (20 mL). Evaporationof the solvent to dryness to afford the crude product that was purifiedon column eluted with EtOAc to give 1.9 g (88%) title product.

[0192] Preparation of (R)-t-Butyl Isobutal Sulfoxide:

[0193] The same procedure was followed using (R)-tert-butyl(1S,2R)-aminoindanol mesitylene sulfonamide sulfinate, and afforded a90% yield.

[0194]¹H NMR (CDCl₃): δ 1.24 (s, 9H), 1.086-1.126 (m, 6H), 2.20-2.30 (m,2H), 2.38-2.45 (m, 1H). ¹³C NMR (CDCl₃): δ 21.78, 23.06, 23.49, 24.12,52.63, 55.00, Anal: Cal: C, 59.20; H, 11.18; S, 19.76. Found: C, 59.39;H, 11.36; S, 19.65.

[0195] Preparation of (S)-t-butyl Methyl Sulfoxide from(2S,4S,5R)-3-(2,4,6-mesitylsulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (One Pot Procedure):

[0196] A solution of(2S,4S,5R)-3-(2,4,6-mesitylsulfonyl)-3,3a,8,8a-tetrahydro-1-oxa-2-thia-3-aza-cyclopenta[a]indene2-oxide (1.44 g, 3.82 mmol) in THF at −15° C. was slowly added tot-BuMgCl (4.0 mL, 1.0M) in THF, and the reaction mixture was stirred(1-2 hours) until the reaction complete as monitored by TLC. Methylmagnesium bromide (4.4 mL, 1.0 M) in THF was then added, the reactionmixture was warmed to room temperature and stirred for 1-2 hours. Thereaction was monitored by TLC. After the reaction mixture was cooled to0° C., the reaction was quenched by addition of saturated aq. NH₄Cl (5mL), stirred and diluted with EtOAc (5 mL). The aqueous phase wasextracted with EtOAc (5 mL×2) and the organic solvent was evaporated.The residue was purified on silica gel eluted with EtOAc/MeOH (8:2) togive the title product (0.38 g, 83%).

[0197] Preparation of (S)-t-butyl Methyl Sulfoxide from (S)-t-Butyl(1S,2R)-norephedrine sulfinate:

[0198] A THF (2 mL) solution of (S)-t-butyl (1S,2R)-norephedrinesulfinate ester (0.25 g) at −78° C. was added MeMgCl (0.4 mL, 3 M) inTHF, and the reaction mixture was warmed slowly to room temperature andstirred. The reaction was monitored by TLC. The reacton was quenchedwith saturated aqueous NH₄Cl (2 mL), diluted with EtOAc (5 mL) and theorganic phase was gently evaporated. The residue was purified on silicagel eluted with EtOAc/MeOH (9:2, v/v) to give 58 mg (79%) title product.

[0199]¹H NMR (CDCl₃): δ 1.25 (s, 9H), 2.38 (s, 3). ¹³C NMR (CDCl₃): δ22.52, 31.60, 52.62.

[0200] Preparation of (S)-picolinyl t-butylsulfoxide from (S)-tert-Butyl(1R,2S)-aminoindanol 4-toluene Sulfonamide Sulfinate:

[0201] To a picolinyl lithium solution (2 mL, 0.6 M) in THF at −78° C.was added (S)-t-butyl-(1R,2S)-aminoindinanol tosylate sulfinate (130 mg,0.30 mmol). The mixture was warmed to room temperature and stirred untilthe starting material was consumed as monitored by TLC. The reaction wasquenched by aq. NaHCO₃ (20 mL) and diluted with ethyl acetate (20 mL),and the organic phase was washed with water (20 mL) and brine (20 mL).The organic layer was concentrated in vacuo and the residue was purifiedby chromatography eluted with ethyl acetate to yield 32 mg of thedesired product.

[0202]¹H NMR (300 MHz, CDCl₃): δ 1.19 (s, 9H), 3.82 (d, 1H, J=12.3 Hz),4.07 (d, 11H, J=12.3 Hz), 7.26 (m, 1H), 7.45 (d, 1H, J=7.2 Hz), 7.72(ddd, 1H, J=7.5, 7.5, 1.8 Hz), 8.63 (dd, 1H, J=4.8, 0.9 Hz). ¹³C NMR (75MHz, CDCl₃): δ 23.29, 54.19, 55.09, 123.19, 132.31, 137.19, 142.77,150.12.

[0203] Preparation of (R)-phenyl t-butylsulfoxide from (S)-tert-Butyl(1R,2S)-aminoindanol Mesitylene Sulfonamide:

[0204] A 50 mL flask was charged with (S)-tertbutyl-(1R,2S)-aminoindanolmesitylene sulfonamide (1.12 g, 3.0 mmol) and THF (3 mL) and the mixturewas cooled to −20° C. To the mixture was added phenylmagnesium bromide(9 mL, 1.0 M in THF), the reaction mixture was stirred at 0° C. and thereaction was monitored by THC. The reaction was quenched by aqueousNaHCO₃ (20 mL) and diluted with ethyl acetate (70 mL), and the organicphase was washed with water (50 mL) and brine (50 mL). The organic layerwas concentrated in vacuo and the residue was purified by chromatographyeluted by 2:1 hexane:ethyl acetate to give 390 mg of (R)-phenylt-butylsulfoxide.

[0205]¹H NMR (300 MHz, CDCl₃): δ 1.20 (s, 9H), 7.53 (m, 3H), 7.63 (m,3H). ¹³C NMR (75 MHz, CDCl₃): δ 23.04, 56.02, 126.57, 128.63, 131.40,140.23. Anal. Calcd for C₁₀H₁₄OS: C, 65.89; H, 7.74; S, 17.59. Found: C,65.91; H, 7.78; S, 17.65. Optical rotation: C=1.0, CHCl₃ [α]²²_(D)=+174.6 (lit.=+175).

[0206] While the invention has been described with respect to particularembodiments, it will be apparent to those skilled in the art thatvarious changes and modifications may be made without departing from thespirit and scope of the invention as defined in the claims. Suchmodifications are also intended to fall within the scope of the appendedclaims.

What is claimed is:
 1. A method of preparing a sulfinamide or sulfoxide,which comprises contacting a compound of Formula 1:

wherein n is 0 to 3; L is CO_(m)R₃ or SO_(m)R₃, wherein m is 0 to 3; R₁and R₂ together form a cyclic structure or each of R₁ and R₂ isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheterocycle; R₁′ and R_(2′) together form a cyclic structure or each ofR_(1′) and R_(2′) is independently hydrogen, substituted orunsubstituted alkyl, substituted or unsubstituted aralkyl, substitutedor unsubstituted heteroalkyl, substituted or unsubstituted aryl, orsubstituted or unsubstituted heterocycle; R_(a) and R_(b) together forma cyclic structure or each of R_(a) and R_(b) is independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted aryl, or substituted or unsubstituted heterocycle; andeach of R₃ and X is independently a polymer bound alkyl, aryl orheteroalkyl, substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aryl, substituted or unsubstituted ether,substituted or unsubstituted ester, substituted or unsubstituted ketone,substituted or unsubstituted phosphonate, substituted or unsubstitutedphosphonic acid ester, substituted or unsubstituted phosphinoyl,substituted or unsubstituted sulfide, substituted or unsubstitutedsulfone, substituted or unsubstituted sulfinyl imine, substituted orunsubstituted heterocycle, or —NR₄R₅, wherein R₄ and R₅ together withthe nitrogen atom to which they are attached form a heterocycle or eachof R₄ and R₅ is independently hydrogen, substituted or unsubstitutedalkyl, substituted or unsubstituted heteroalkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle; with a compound of formula MY,wherein M is a metal or metal complex capable of transferring Y to thepositively charged sulfur atom of the compound of Formula 1 and Y isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aryl, substituted or unsubstituted ether,substituted or unsubstituted ester, substituted or unsubstituted ketone,substituted or unsubstituted phosphonate, substituted or unsubstitutedphosphonic acid ester, substituted or unsubstituted phosphinoyl,substituted or unsubstituted sulfide, substituted or unsubstitutedsulfone, substituted or unsubstituted sulfinyl imine, substituted orunsubstituted heterocycle, or is of the formula —NR₆R₇, wherein R₆ andR₇ together with the nitrogen atom to which they are attached form aheterocycle or each of R₆ and R₇ is independently a polymer bound alkyl,aryl or heteroalkyl; hydrogen; substituted or unsubstituted alkyl;substituted or unsubstituted aralkyl; substituted or unsubstitutedheteroalkyl; substituted or unsubstituted aryl; substituted orunsubstituted ether; substituted or unsubstituted ester; substituted orunsubstituted ketone; substituted or unsubstituted phosphonate;substituted or unsubstituted phosphonic acid ester; substituted orunsubstituted phosphinoyl; substituted or unsubstituted sulfide;substituted or unsubstituted sulfone; substituted or unsubstitutedsulfinyl imine; substituted or unsubstituted heterocycle; underconditions suitable for the formation of a compound of Formula 2:


2. The method of claim 1 wherein the compound of Formula 1 isstereomerically pure.
 3. The method of claim 1 wherein the compound ofFormula 2 is stereomerically pure.
 4. The method of claim 1 wherein M ofthe formula MY is Al, Ba, Li, Na, K, Ti, Mg, Mn, Zn, Cd, In, Cu, or isof the formula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ, or CuZ, Ti(OR₁)₃Z,Ti(OR₁)₄,wherein Z is Cl, Br, I, aryl, alkyl, heteroalkyl, aralkyl, orheterocycle and R₁ is substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheterocycle.
 5. The method of claim 1 wherein the compound of Formula 1is prepared by contacting a compound of Formula 3:

with a compound of the formula M′X, wherein M′ is a metal or metalcomplex capable of transferring X to the positively charged sulfur atomof the compound of Formula
 3. 6. The method of claim 5, wherein M′ ofthe formula M′X is Al, Ba, Li, Na, K, Ti, Mg, Mn, Zn, Cd, In, Cu, or isof the formula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′₂, MnZ′, InZ′, or CuZ′,Ti(OR₁)₃Z′, Ti(OR₁)₄, wherein Z′ is Cl, Br, I, aryl, alkyl, heteroalkyl,aralkyl, or heterocycle and R₁ is substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted aryl, substituted orunsubstituted heterocycle.
 7. The method of claim 5, wherein X istert-butyl, trialkylmethyl, triheteroalkylmethyl, triarylmethyl,triheteroarylmethyl, triheterocyclemethyl, aryl, heterocyclic,heteroaryl, alkyltrialkyl, alkylheteroalkylmethyl, diarylalkylmethyl,adamantyl, dialkyladamantyl, trialkylaryl, triethylmethyl,dimethylethyl, trimethylphenyl, trialkylphenyl, triisopropylphenyl,polymer bound alkyl or aryl or is of Formula 4:

or a salt thereof, wherein each R₈ is independently substituted orunsubstituted alkyl, substituted or unsubstituted aralkyl, substitutedor unsubstituted aryl, substituted or unsubstituted ether, substitutedor unsubstituted sulfide, substituted or unsubstituted heterocycle, aprimary, secondary, or tertiary amine, or a halogen atom; and p is aninteger of 0 to 4; or is of Formula 5:

wherein each R₉ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, a primary, secondary,or tertiary amine, or a halogen atom; and q is an integer of 0 to
 4. 8.The method of claim 7 wherein X is of Formula 4 and p is 0 or
 1. 9. Themethod of claim 8 wherein p is 1 and R₈ is —OCH₃ or —OCHF₂.
 10. Themethod of claim 7 wherein X is of Formula 5, q is 2, and each R₉ is—CH₃, —OCH₃, —OCH₂CF₃, or —OC₅H₁₁.
 11. The method of claim 7 wherein Xis of Formula 5, q is 3, and R₉ is —CH₃ or —OCH₃.
 12. The method ofclaim 1 wherein Y is —NR₆R₇ or is of Formula 4:

or a salt thereof, wherein each R₈ is independently substituted orunsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, a primary, secondary,or tertiary amine, or a halogen atom; and p is an integer of 0 to 4; oris of Formula 5:

wherein each R₉ is independently substituted or unsubstituted alkyl,substituted or unsubstituted heteroalkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, substituted or unsubstitutedether, substituted or unsubstituted sulfide, substituted orunsubstituted heterocycle, a primary, secondary, or tertiary amine, or ahalogen atom; and q is an integer of 0to
 4. 13. The method of claim 12wherein Y is of Formula 4 and p is 0 or
 1. 14. The method of claim 13wherein p is 1 and R₈ is —OCH₃ or —OCHF₂.
 15. The method of claim 12wherein Y is of Formula 5, q is 2, and each R₉ is —CH₃, —OCH₃, —OCH₂CF₃,or —OC₅H₁₁.
 16. The method of claim 12 wherein Y is of Formula 5, q is3, and R₉ is —CH₃ or —OCH₃.
 17. The method of claim 1 wherein R₁ is arylor alkyl.
 18. The method of claim 1 wherein R₂ is aryl or alkyl.
 19. Themethod of claim 1 wherein R₃ is a substituted or unsubstituted loweralkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted heteroalkyl, or aryl.
 20. The method of claim 19 whereinR₃ is 3-mesityl, tolyl, triisopropyl, or a polymer bound alkyl or aryl.21. The method of claim 1 wherein the compound of Formula 1 has one ofthe following structures:

wherein each R₁₀ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, a primary, secondary, or tertiary amine, a heterocycle, or ahalogen atom; n is an integer of 1 to 4; and m is an integer of 0 to 4,and wherein X is tert-butyl, trialkylmethyl, triheteroalkylmethyl,triarylmethyl, triheteroarylmethyl, triheterocyclemethyl, aryl,heterocyclic, heteroaryl, alkyltrialkyl, alkylheteroalkylmethyl,diarylalkylmethyl, adamantyl, dialkyladamantyl, trialkylaryl,triethylmethyl, dimethylethyl, trimethylphenyl, trialkylphenyl,triisopropylphenyl, polymer bound alkyl or aryl or is of Formula 4:

or a salt thereof, wherein each R₈ is independently substituted orunsubstituted alkyl, substituted or unsubstituted aralkyl, substitutedor unsubstituted aryl, substituted or unsubstituted ether, substitutedor unsubstituted sulfide, substituted or unsubstituted heterocycle, aprimary, secondary, or tertiary amine, or a halogen atom; and p is aninteger of 0 to 4; or is of Formula 5:

wherein each R₉ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, a primary, secondary,or tertiary amine, or a halogen atom; and q is an integer of 0 to
 4. 22.The method of claim 1 wherein the compound of Formula 2 is of one of thefollowing formulas:

wherein R₆ and R₇ together with the nitrogen atom to which they areattached form a heterocycle or each of R₆ and R₇ is independently apolymer bound alkyl, aryl or heteroalkyl; hydrogen; substituted orunsubstituted alkyl; substituted or unsubstituted aralkyl; substitutedor unsubstituted heteroalkyl; substituted or unsubstituted aryl;substituted or unsubstituted ether; substituted or unsubstituted ester;substituted or unsubstituted ketone; substituted or unsubstitutedphosphonate; substituted or unsubstituted phosphonic acid ester;substituted or unsubstituted phosphinoyl; substituted or unsubstitutedsulfide; substituted or unsubstituted sulfone; substituted orunsubstituted sulfinyl imine; substituted or unsubstituted heterocycle;23. The method of claim 22 wherein X is tert-butyl, trialkylmethyl,triheteroalkylmethyl, triarylmethyl, triheteroarylmethyl,triheterocyclemethyl, aryl, heterocyclic, heteroaryl, alkyltrialkyl,alkylheteroalkylmethyl, diarylalkylmethyl, adamantyl, dialkyladamantyl,trialkylaryl, triethylmethyl, dimethylethyl, trimethylphenyl,trialkylphenyl, triisopropylphenyl, polymer bound alkyl or aryl or is ofFormula 4:

or a salt thereof, wherein each R₈ is independently substituted orunsubstituted alkyl, substituted or unsubstituted aralkyl, substitutedor unsubstituted aryl, substituted or unsubstituted ether, substitutedor unsubstituted sulfide, substituted or unsubstituted heterocycle, aprimary, secondary, or tertiary amine, or a halogen atom; and p is aninteger of 0 to 4; or is of Formula 5:

wherein each R₉ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, a primary, secondary,or tertiary amine, or a halogen atom; and q is an integer of 0 to
 4. 24.The method of claim 22 wherein at least one of R₆ and R₇ is hydrogen.25. The method of claim 24 wherein R₆ and R₇ are both hydrogen.
 26. Themethod of claim 5 wherein the compound of Formula 3 has one of thefollowing structures:

wherein each R₁₀ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, a primary, secondary, or tertiary amine, a heterocycle, or ahalogen atom; n is an integer of 1 to 4; and m is an integer of 0 to 4,and wherein R₃ is aryl, alkyl, or a polymer bound aryl or alkyl.
 27. Amethod of preparing pantoprazole or a derivative, prodrug, salt,solvate, clathrate, or stereomerically pure form thereof, whichcomprises contacting a compound of Formula 11:

wherein R₁ and R₂ together form a cyclic structure or each of R₁ and R₂is independently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted heterocycle; R_(1′) and R_(2′) together form a cyclicstructure or each of R_(1′) and R_(2′) is independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, or substituted orunsubstituted heterocycle; and Prot is a protecting group; with acompound of Formula 12:

wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ, or CuZ, and Z is Cl, Br, I,aryl, aralkyl, or heterocycle; under conditions suitable for theformation of a compound of Formula 13:

and optionally contacting the compound of Formula 13 with a reagentcapable of replacing Prot with a hydrogen atom or a cation.
 28. Themethod of claim 27 wherein the compound of Formula 11 is prepared bycontacting a compound of Formula 3 with a compound of Formula 14:

wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′₂, MnZ′, InZ′, or CuZ′, and Z′ isCl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficientfor the formation of the compound of Formula
 11. 29. The method of claim27 wherein the compounds of formulas 11 and 13 are enantiomericallypure.
 30. A method of preparing lansoprazole or a derivative, prodrug,salt, solvate, clathrate, or stereomerically pure form thereof, whichcomprises contacting a compound of Formula 15:

wherein R₁ and R₂ together form a cyclic structure or each of R₁ and R₂is independently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted heterocycle; R_(1′) and R_(2′) together form a cyclicstructure or each of R_(1′) and R_(2′) is independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, or substituted orunsubstituted heterocycle; and Prot is a protecting group; with acompound of Formula 16:

wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ, or CuZ, and Z is Cl, Br, I,aryl, aralkyl, or heterocycle; under conditions suitable for theformation of a compound of Formula 17:

and optionally contacting the compound of Formula 17 with a reagentcapable of replacing Prot with a hydrogen atom or a cation.
 31. Themethod of claim 30 wherein the compound of Formula 15 is prepared bycontacting a compound of Formula 3:

with a compound of Formula 18:

wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′₂, MnZ′, InZ′, or CuZ′, and Z′ isCl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficientfor the formation of the compound of Formula
 15. 32. The method of claim30 wherein the compounds of formulas 15 and 17 are enantiomericallypure.
 33. A method of preparing omeprazole or a derivative, prodrug,salt, solvate, clathrate, or stereomerically pure form thereof whichcomprises contacting a compound of Formula 19:

wherein R₁ and R₂ together form a cyclic structure or each of R₁ and R₂is independently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted heterocycle; R_(1′) and R_(2′) together form a cyclicstructure or each of R_(1′) and R_(2′) is independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, or substituted orunsubstituted heterocycle; and Prot is a protecting group; with acompound of Formula 20:

wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ′, or CuZ, and Z is Cl, Br, I,aryl, aralkyl, or heterocycle; under conditions suitable for theformation of a compound of Formula 21:

and optionally contacting the compound of Formula 21 with a reagentcapable of replacing Prot with a hydrogen atom or a cation.
 34. Themethod of claim 33 wherein the compound of Formula 19 is prepared bycontacting a compound of Formula 3:

with a compound of Formula 22:

wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′₂, MnZ′, InZ′, or CuZ′, and Z′ isCl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficientfor the formation of the compound of Formula
 19. 35. The method of claim33 wherein the compounds of formulas 19 and 21 are enantiomericallypure.
 36. A method of preparing rabeprazole or a derivative, prodrug,salt, solvate, clathrate, or stereomerically pure form thereof, whichcomprises contacting a compound of Formula 15:

wherein R₁ and R₂ together form a cyclic structure or each of R₁ and R₂is independently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted heterocycle; R_(1′) and R_(2′) together form a cyclicstructure or each of R_(1′) and R_(2′) is independently hydrogen,substituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, or substituted orunsubstituted heterocycle; and Prot is a protecting group; with acompound of Formula 23:

wherein M is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ, BaZ, MgZ, ZnZ, AlZ₂, MnZ, InZ, or CuZ, and Z is Cl, Br, I,aryl, aralkyl, or heterocycle; under conditions suitable for theformation of a compound of Formula 24:

and optionally contacting the compound of Formula 24 with a reagentcapable of replacing Prot with a hydrogen atom or a cation.
 37. Themethod of claim 36 wherein the compound of Formula 15 is prepared bycontacting a compound of Formula 3:

with a compound of Formula 18:

wherein M′ is Al, Ba, Li, Na, K, Mg, Mn, Zn, Cd, In, Cu, or is of theformula CdZ′, BaZ′, MgZ′, ZnZ′, AlZ′₂, MnZ′, InZ′, or CuZ′, and Z′ isCl, Br, I, aryl, aralkyl, or heterocycle; under conditions sufficientfor the formation of the compound of Formula
 23. 38. The method of claim36 wherein the compounds of formulas 23 and 25 are enantiomericallypure.
 39. A compound of Formula 7:

or a salt, solvate, clathrate, or stereomerically pure form thereof,wherein R₃ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, or —NR₄R₅, wherein R₄and R₅ together with the nitrogen atom to which they are attached form aheterocycle or each of R₄ and R₅ is independently hydrogen, isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle; each R₁₀ is independentlysubstituted or unsubstituted alkyl, substituted or unsubstitutedaralkyl, substituted or unsubstituted aryl, substituted or unsubstitutedether, substituted or unsubstituted sulfide, a primary, secondary, ortertiary amine, a heterocycle, or a halogen atom; n is an integer of 1to 4; and m is an integer of 0 to
 4. 40. A compound of Formula 25:

or a salt, solvate, clathrate, or stereomerically pure form thereof,wherein R₁ and R₂ together form a cyclic structure or each of R₁ and R₂is independently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, or substitutedor unsubstituted heterocycle; R₃ is substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, substituted or unsubstituted heterocycle, or —NR₄R₅, wherein R₄and R₅ together with the nitrogen atom to which they are attached form aheterocycle or each of R₄ and R₅ is independently hydrogen, substitutedor unsubstituted alkyl, substituted or unsubstituted aralkyl,substituted or unsubstituted aryl, substituted or unsubstituted ether,substituted or unsubstituted sulfide, or substituted or unsubstitutedheterocycle; each R₁₁ is independently substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, a primary, secondary, or tertiary amine, aheterocycle, or a halogen atom; R₁₂ is substituted or unsubstitutedalkyl, substituted or unsubstituted aralkyl, substituted orunsubstituted aryl, substituted or unsubstituted ether, substituted orunsubstituted sulfide, or substituted or unsubstituted heterocycle, oris a sulfoxide; and r is an integer from 0 to
 4. 41. The compound ofclaim 40 wherein said compound is of Formula 26:

or a salt, solvate, clathrate, or stereomerically pure form thereof,wherein each R₁₁ is independently substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, a primary, secondary, or tertiary amine, a heterocycle, or ahalogen atom; R₁₂ is substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, substituted orunsubstituted ether, substituted or unsubstituted sulfide, orsubstituted or unsubstituted heterocycle, or is a sulfoxide; and r is aninteger from 0 to
 4. 42. A compound of Formula 9:

or a salt, solvate, clathrate, or stereomerically pure form thereof,wherein R₃ is independently a polymer bound alkyl, aryl or heteroalkyl;substituted or unsubstituted alkyl; substituted or unsubstitutedaralkyl; substituted or unsubstituted heteroalkyl; substituted orunsubstituted aryl; substituted or unsubstituted ether; substituted orunsubstituted ester; substituted or unsubstituted ketone; substituted orunsubstituted phosphonate; substituted or unsubstituted phosphonic acidester; substituted or unsubstituted phosphinoyl; substituted orunsubstituted sulfide; substituted or unsubstituted sulfone; substitutedor unsubstituted sulfinyl imine; substituted or unsubstitutedheterocycle; or —NR₄R₅, wherein R₄ and R₅ together with the nitrogenatom to which they are attached form a heterocycle or each of R₄ and R₅is independently hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, or substituted or unsubstituted heterocycle.
 43. A compound ofFormula 10:

or a salt, solvate, clathrate, or stereomerically pure form thereof,wherein R₃ is independently a polymer bound alkyl, aryl or heteroalkyl;substituted or unsubstituted alkyl; substituted or unsubstitutedaralkyl; substituted or unsubstituted heteroalkyl; substituted orunsubstituted aryl; substituted or unsubstituted ether; substituted orunsubstituted ester; substituted or unsubstituted ketone; substituted orunsubstituted phosphonate; substituted or unsubstituted phosphonic acidester; substituted or unsubstituted phosphinoyl; substituted orunsubstituted sulfide; substituted or unsubstituted sulfone; substitutedor unsubstituted sulfinyl imine; substituted or unsubstitutedheterocycle; or —NR₄R₅, wherein R₄ and R₅ together with the nitrogenatom to which they are attached form a heterocycle or each of R₄ and R₅is independently hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, or substituted or unsubstituted heterocycle; each R₁₀ isindependently substituted or unsubstituted alkyl, substituted orunsubstituted aralkyl, substituted or unsubstituted aryl, a primary,secondary, or tertiary amine, or a halogen atom; n is an integer of 1 to4; and m is an integer of 0 to
 4. 44. A compound of Formula 56:

or a salt, solvate, clathrate, or stereomerically pure form thereof,wherein R₃ is independently a polymer bound alkyl, aryl or heteroalkyl;substituted or unsubstituted alkyl; substituted or unsubstitutedaralkyl; substituted or unsubstituted heteroalkyl; substituted orunsubstituted aryl; substituted or unsubstituted ether; substituted orunsubstituted ester; substituted or unsubstituted ketone; substituted orunsubstituted phosphonate; substituted or unsubstituted phosphonic acidester; substituted or unsubstituted phosphinoyl; substituted orunsubstituted sulfide; substituted or unsubstituted sulfone; substitutedor unsubstituted sulfinyl imine; substituted or unsubstitutedheterocycle; or —NR₄R₅, wherein R₄ and R₅ together with the nitrogenatom to which they are attached form a heterocycle or each of R₄ and R₅is independently hydrogen, substituted or unsubstituted alkyl,substituted or unsubstituted aralkyl, substituted or unsubstituted aryl,substituted or unsubstituted ether, substituted or unsubstitutedsulfide, or substituted or unsubstituted heterocycle.
 45. The compoundof claim 39, 40, 42, 43, 44, or 45 wherein said compound isstereomerically pure.